Effects of Levetiracetam an Antiepileptic Drug on the Multi-biological Parameters in African catfish Clarias gariepinus (Burchell, 1822)

Effects of Levetiracetam an Antiepileptic Drug on the Multi-biological Parameters in African catfish Clarias gariepinus (Burchell, 1822) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effects of Levetiracetam an Antiepileptic Drug on the Multi-biological Parameters in African catfish Clarias gariepinus (Burchell, 1822) Joy Ihuoma Nzei, Ekenma Julia Agwu, Perpetua Ebube Uba, Inwelegbu Valentine Chukwuemeka This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4523849/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Mar, 2025 Read the published version in Environmental Science and Pollution Research → Version 1 posted 5 You are reading this latest preprint version Abstract This study investigated the impact of levetiracetam on the multi-biological parameters in juvenile Clarias gariepinus . Fish were exposed to 0.2, 0.6, and 0.8mg/L of levetiracetam and filtered dechlorinated water (control) for 10 days, followed by a recovery period of 5 days. Blood samples were collected periodically for haematological and serum biochemical profiling, and the fish were sacrificed for the liver and brain tissues' analysis. Skin colouration, mucus secretion, and air-gulping increased with concentration and duration of exposure, while swimming rate and opercular movement decreased. A significant ( p < 0.05) dose- and duration-dependent decrease was recorded in the red blood cells, packed cell volume, haemoglobin, and white blood cell counts, while the opposite was recorded in the mean corpuscular haemoglobin, volume, and haemoglobin concentrations. Compared to the control, there were no significant differences in the values of the differential leukocyte counts, except for lymphocytes, which were significantly ( p < 0.05) lower in the highest concentration at the end of the exposure period. Aspartate and alanine aminotransferase, and alkaline phosphatase activities increased significantly (p < 0.05), while the values for protein and glucose were reduced compared to the control. The oxidative stress biomarkers, liver catalase, superoxide dismutase, and glutathione peroxidase activities decreased significantly (p < 0.05), while malondialdehyde and acetylcholinesterase activities increased significantly (p < 0.05) compared to the control. The activities were duration- and concentration-dependent. No significant difference in the correction factor, while the hepatosomatic index decreased significantly (p < 0.05) compared to the control. The parameters returned to normal after post 5-day withdrawal of levetiracetam administration. The study indicated that levetiracetam is toxic to fish. Fish levetiracetam morphometric and biochemical changes haematology antioxidants Figures Figure 1 Figure 2 1.0 Introduction The widespread use of pharmaceuticals and their subsequent release into aquatic ecosystems, has raised concerns about their potential eco-toxicological impact on non-target organisms (Ebele 2020). Levetiracetam, an antiepileptic drug (AED), chemically known as (S)-ethyl-2-oxo-1-pyrrolidineacetamide and an analogue of the neurotransmitter γ-aminobutyric acid (GABA), is commonly used due to its favourable pharmacokinetic profile and low incidence of adverse effects in humans (Cereghino et al. 2000 ). It is also used off-label for the prophylaxis of traumatic brain injury (TBI) and supratentorial neurosurgery (Jones et al. 2008 ). It is not extensively metabolized and has a low potential for drug interactions involving hepatic enzymes. This characteristic makes it a favourable choice for patients taking multiple medications, as it is less likely to interfere with the metabolism of other drugs (Cereghino et al. 2000 ). Levetiracetam is eliminated through the kidneys, through urine unchanged (Perucca and Bialer 1996 ) and can enter water bodies through various channels including human and animal excretion, hospital waste/discharge/effluents, landfills leachates (Bilbao-Meseguer et al. 2021 ) and agricultural runoffs into the ground and surface water and in the aquatic environment, through dilution, degradation, and adsorption can find their way into the tissues of aquatic organisms (Zhu et al. 2023 ), having the potential to impact the aquatic life and beyond. Studies have shown that some pharmaceuticals, including AEDs are toxic to aquatic organisms including fish. Carbamazepine was harmful to aquatic microalgal species (Haase et al. 2015 ), Daphnia magna (Oliveira et al. 2015 ), Carassius auratus (Li et al. 2008 )d gariepinus (Ogueji et al. 2017a ). It has also suppressed steroidogenesis in organisms (Hinfray et al. 2011 ; Wassmur et al. 2013 ). Diazepam is toxic to C. clariepinus (Ogueji et al. 2017b ), diclofenac to Oreochromis sp. (Krishnapriya et al. 2017 ), zebrafish (Bio and Nunes 2020 ) and biphenol to Indian major carp Labeo rhita (Krishnapriya et al. 2017 ). Aquatic organisms, including fish, play vital roles in ecosystem dynamics and can serve as indicators of environmental health. Studying the effects of pharmaceuticals on these organisms is crucial to understanding their potential ecological consequences (Klanovicz et al. 2021). Exposure to pharmaceuticals in the aquatic system can cause biological changes in organisms, especially fish. These changes are called biomarkers and are used as indicators of exposure to environmental pollutants. These biomarkers enable the rapid assessment of the health of organisms and warn about possible environmental risks (Van der Oost et al. 2003 ). The presence of levetiracetam in aquatic environments has been detected, and its effects on aquatic organisms, particularly fish species, remain poorly understood (Pieróg et al. 2021 ). Literature on the toxicological effects of levetiracetam on freshwater fishes is scanty. This is because levetiracetam is a second-generation antiepileptic drug, i.e. it is new in the market (Sabaa et al. 2020 ; Suzuki et al. 2023 ). In Nigeria, no research to the best of our knowledge has been published on the effects of levetiracetam on freshwater fishes in the aquatic ecosystem. The African catfish C. gariepinus is one the commercial indigenous fish species preferred due to its fast growth, nutritional quality, easy domestication, high reproductive potential and adaptability to extreme water quality conditions (Maranga et al. 2023 ). These qualities make C. gariepinus highly popular amongst aquaculture farmers and also a vital organism in ecosystem dynamics, as it can serve as an indicator of environmental health. Thus, this study was aimed at investigating the sub-lethal effects of levetiracetam on the behaviour, haematological, biochemical, lipid peroxidation, oxidative stress and biometric parameters of C. gariepinus and the recovery ability of the fish post-drug exposure. 2.0 Materials and Methods Fish sampling and management C. gariepinus juveniles (n = 306), of mean length 9.01 ± 9 cm and weight, 6.67 ± 2.24 g were procured from Freedom Fisheries Limited Farm, Nsukka, Enugu State and were transported to the Zoological Garden of the Department of Zoology and Environmental Biology, University of Nigeria, Nsukka. The fish were kept in 5 plastic bowls (20 litres), containing 10L of filtered de-chlorinated water. During the acclimatization and sub-lethal exposure period, the fish were fed a commercial standard diet of dry pellet feed (Aller Aqua Nigeria limited) at 3% body weight per day, and the water changed every 24 h just before feeding. They were fed daily (8–10 am).The study was carried out in an indoor experimental system, within normal photoperiod of day/night (14:10) cycle common at Nsukka, Nigeria, and the fish were sustained at temperature of 26.0 ± 1°C, pH of 7.5 ± 0.5, and dissolved oxygen of 97% saturation. All the animal procedures were performed per the standards outlined in the guidelines for the care and use of experimental animals by the research ethical committee of the University of Nigeria, Nsukka. The fish were acclimatized for 14 days to laboratory conditions before starting the experiment. All the test procedures adhered to OECD guideline 215 (OECD 2000) and were conducted under conditions similar to acclimation. Test drug Commercial pharmaceutical preparations of the anti-epileptic drug with the trade name Suvitra, containing 500 mg of levetiracetam as the active pharmaceutical ingredient (API) in a tablet (Micro Labs Limited, India) was used. A stock solution of the drug was prepared by dissolving 10 tablets containing 500 mg of levetiracetam (as the active ingredient) each in 10 L of the filtered, dechlorinated water. The stock solution was used in preparing the test solutions with nominal concentrations of levetiracetam. Design of experiments for acute exposure and LC 50 A range finding test was carried out, and the appropriate range of levetiracetam concentrations (12.5 and 62.5 mg/L) that can cause percentage mortalities of 0% and 100%, respectively, was selected. From the obtained range values, ten fish each from the acclimatized batch were then exposed to five (12.5, 25.0, 37.5, 50.0, and 62.5 mg/L) nominal concentrations of levetiracetam and distilled water only (0 mg/L), for the control. The experimental setup and control were replicated three times for strong statistical analysis. The fish were not fed during the acute toxicity studies to prevent interference from faeces. The 24, 48, 72, and 96h survival and mortality rates were noted. Forceps were used to remove the dead fish immediately to prevent deterioration of the test media. Before removal of the fish, they were regarded as dead when their operculum stopped beating. The LC 50 at the end of the 96 h experimental duration, was determined by probit analysis (Finney 1971 ), using SPSS 23.0. Sub-lethal levetiracetam administration The 96h median concentration (LC 50 ) of levetiracetam was calculated to be 37.54 mg/L, according to the probit analysis. Based on the 96 h LC 50 , three different sub-lethal concentrations (0.2, 0.6 and 0.8 mg/L) were selected for the sub-lethal exposure. A total of 120 acclimated fish were used without regard to sex. The fish were not fed 24 hours before the commencement of the experiment. Three treatment concentrations were used for the experiment namely, 0.2, 0.6, 0.8 mg/L of levetiracetam and non- chlorinated tap water only (control). Ten (10) fish each were placed into 4 (four) fresh glass aquaria (60 × 30 × 30 cm size), labelled A-D. Aquarium A contained 10 L of non- chlorinated tap water only (control), while B, C and D contained 10 L of 0.8, 0.6 and 0.2 mg/L of levetiracetam, respectively. The experimental arrangement was replicated three times, making it a total of 30 fish and 3 aquaria for each treatment concentration and the control.A plastic plant (place of refuge) was placed in each of the glass aquarium, to test the effect of levetiracetam on fish behavioural response to refuge. The experiment was conducted in a static renewal bioassay system in which the water and levetiracetam were changed daily to maintain constant drug concentration. The set-up lasted for 10 days and another 5 days for recovery. Fish in the treatment groups were transferred to aquaria with only de-chlorinated water The fish were fed a small quantity of feed, approximately 3% of the body weight an hour before changing the water and leviteracetam, to avoid mortality arising from starvation. There were no mortalities during the 15-day exposure period. Observations of the behavioural and stress-related responses and clinical signs of toxicity of C. gariepinus juveniles exposed to the drug were made at the end of the 10-day treatment and 5-day recovery period. Three (3) fishes from each of the experimental and control groups were removed for sampling at the end of day 1, 5, 10 and 15. Blood was collected, and the fish was sacrificed. The liver and brain tissues were excised, weighed, and washed in ice-cold buffer for all the various treatments and intervals. The minced tissues were rinsed clear of blood with cold isolation buffer and homogenized on ice in a glass Potter-Elvehjem homogenizing vessel with a motor-driven pestle. The isolation buffer contained 100 mM Tris-HCl and pH of 7.20 was adjusted with HCl. The liver was used for the oxidative stress and antioxidant enzymes, while the brain was used for the activities of the acetylcholinesterase. Blood sample collection 1.0 ml of blood was collected on each sampling day (days 1, 5, 10, and 15), from the three randomly selected fish from each of the treatment groups and the control by cardiac puncture, using a hypodermic heparinized syringe. Half was transferred to an EDTA container to avoid clotting, and used for the estimation of the haematological parameters, while the remaining half was centrifuged at 10000 g at 4°C for 20 min to separate the plasma which was used for the estimation of biochemical parameters. Haematological assays Following blood collection, the haematological parameters including red blood cell (RBC), packed cell volume (PCV) also known as haematocrit, haemoglobin (Hb), white blood cells (WBC), Mean Corpuscular volume (MCV), Mean corpuscular haemoglobin concentration (MCHC) and Mean corpuscular haemoglobin (MCH), and differential white blood counts were assessed. RBC counts were estimated using a Neubauer hemocytometer, as described by Rusia and Sood ( 1992 ). Briefly, 0.02 mL of blood was pipetted from the blood sample and added to 4 mL of the RBC diluting fluid (Toisson’s solution) in a clean test tube to make a 1:200 dilution of the blood sample. The diluted blood sample was loaded onto a Neubauer counting chamber, and all RBCs in the five groups of 16 small squares in the central area of the Neubauer chamber were counted using a light microscope under a high power (40 X) objective. The number of cells counted for each sample was multiplied by 10,000 to obtain the RBC count per microliter of blood. Hematocrit (PCV) was determined using the microhematocrit method of Nwani et al. ( 2013a ), Hb determination was done using the cyanmethemoglobin method by Blaxhall and Daisley ( 1973 ), determination of leucocytes was by Rusia and Sood ( 1992 ). Counting the numbers of different types of leucocytes (neutrophils, monocytes, lymphocytes, eosinophils, and basophils) in the blood smears was identified as described by Anderson ( 2003 ). The number of each type of leukocyte was calculated as a percentage. Erythrocyte indices, such as MCHC, MCH and MCV, were calculated from the results of RBC count, WBC count, Hb, and PCV (Bain et al. 2016 ) according to standard formulae: $$\:\text{M}\text{C}\text{V}\:(\text{f}\text{l}/\text{c}\text{e}\text{l}\text{l})=\frac{\text{P}\text{C}\text{V}\:\left(\text{\%}\right)\:\text{X}\:10}{RBC\:count\:in\:millions/L\:}$$ $$\:\text{M}\text{C}\text{H}\text{C}\:(\text{g}/\text{d}\text{l})=\frac{\text{H}\text{b}\:\left(\frac{\text{g}}{\text{d}\text{l}}\right)\:\text{X}\:100}{\text{P}\text{C}\text{V}\:\left(\text{\%}\right)\:}$$ $$\:\text{M}\text{C}\text{H}\:(\text{p}\text{g}/\text{c}\text{e}\text{l}\text{l})=\frac{\text{H}\text{b}\:\left(\frac{\text{g}}{\text{d}\text{l}}\right)\:\text{X}\:10}{RBC\:count\:in\:millions/L\:}$$ Biochemical Indices Randox diagnostic kits were used for biochemical tests. The activities of aspartate and alanine aminotransferase, alkaline phosphatase, protein, and glucose levels were assayed by the method of Reitman and Frankel ( 1957 ) as outlined in the Randox kit. Assay of Oxidative Stress, Antioxidant Enzymes and acetylcholinesterase activity The Catalase (CAT) activity was determined according to the method described by Aebi ( 1984 ). Superoxide dismutase (SOD) activity was determined by measuring the inhibition of antioxidation of epinephrine at pH 10.02 at 30 o C (Arthur and Boyne, 1985 ). The activity of glutathione peroxidase (GPx) was measured by the method of Lawrence and Buck (1976), with the specific activity being determined using the extinction coefficient of 6.22 mM/cm. Malondialdehyde (MDA) an index of lipid peroxidation was determined using the method of Buege and Aust ( 1978 ). The acetylcholinesterase activity was determined by the methods of Birman ( 1985 ). Morphometric variations During each sampling period, the standard length and body weight of the fish were determined. The weight of the excised liver previously documented was used. Following the methods of White and Fletcher ( 1985 ), the condition factor (CF) and hepatosomatic index (HSI) were calculated as: CF = (Body weight (g)/Standard length (cm) 3 ) x 100 HSI = (Liver weight (g)/Body weight (g)) x 100 Statistical analysis All data were analysed using one-way analysis of variance (ANOVA) using SPSS (version 22.0) followed by Duncan’s multiple range post-hoc test. Differences were considered significant at p ≤ 0.05. Results were presented as mean ± standard deviation (SD). 3. 0 Results 3.1 Changes in the behaviour of C. gariepinus exposed to levetiracetam Abnormal behavioural responses such as loss of balance, increased mucus secretion, unprecedented swimming, air gulping, and opercular movement rates were documented in the treated fish. At lower concentrations, swimming and opercula movement rates were faster and slower at high concentrations of 0.8 mg/L. Conversely, air gulping, loss of equilibrium, jerky movement, mucus secretion, and skin discolouration increased at higher concentrations during sublethal exposure of C. gariepinus to levetiracetam as shown in Table 1 . In addition, at low levels of the drug, the fish were also swimming close to the edge of the tanks, but as concentration increased, they avoided the edge of the tanks (Table 1 ). After 5 days of recovery, the observed abnormalities reduced greatly, especially for the lower concentrations, but not to the levels of the control. Table 1 Changes in the behaviour of C. gariepinus after 10 days of exposure to a sub-lethal concentration of levetiracetam and 5- days recovery period Exposure duration Parameters Control Levetiracetam concentration (mg/L) 0.2 0.6 0.8 10 days Skin discoloration - ++ ++ +++ Loss of equilibrium - + ++ +++ Mucus secretion - ++ ++ +++ Swimming rate - ++ ++ + Jerky swimming movement - + + ++ Operculum movement - ++ + + Air gulping - + ++ ++ Avoiding the edge of the tank - - + +++ 5-d withdrawal Skin discoloration - - + ++ Loss of equilibrium - - + ++ Mucus secretion - - + ++ Swimming rate - + + + Jerky swimming movement - - + + Operculum movement - + + + Air gulping - - + + Avoiding the edge of the tank - - + ++ Key: ‘-’ indicates normal behavior/absent, ‘+’ mild, ‘++’ moderate, and ‘+++’ high 3.2 Haematological changes in C. gariepinus exposed to sub-lethal concentrations of levetiracetam The effects of levetiracetam on the haematological profiles PCV, RBC, Hb, WBC, MCH and MCHC, are presented in Table 2 . Levetiracetam significantly ( p < 0.05) decreased PCV, RBC, WBC and Hb values of the treated fish in a concentration - and duration - dependent manner compared to the control. There was a concentration-dependent decrease in the PCV in C. gariepinus exposed to levetiracetam form day 5 to 10, but only in the higher concentrations 0.6 and 0.8 mg/L. At the end of the 10 - days exposure period, PCV values ranged from 36.00 ± 3.46 to 26.67 ± 1.53% for the control and 0.8 mg/L concentration exposed fis respectively. After the 5- day recovery period, the PCV was still significantly ( p < 0.05) decreased in the treated fish. The RBC counts significantly ( p < 0.05) decreased in a concentration - and duration - dependent manner from day 5 to 10 for the fish exposed to all concentrations. RBC values ranged from 9.75 ± 0.06 to 6.21 ± 0.17 x10 12 /L for the control fish and the .0.8 mg/L exposed fish respectively. The pattern encountered for RBC counts of treated fish, was observed for Hb and WBC. Hb values of the fish decreased from 9.07 ± 0.12 to 7.23 ± 0.21 g/dL, while those for WBC decreased from 8467 ± 493 to 7383 ± 252 x10 6 /L for the control and 0.8 mg/L exposed fish respectively, at the end of the 10 days exposure period. After 5 days of recovery, RBC, Hb and WBC levels in the fish exposed to various concentrations of the drug, were still reduced when compared to the control. This observed reduction was only significant ( p < 0.05) for WBC and at all concentrations. The results of the erythrocyte indices (MCH, MCV and MCHC) of the treated fish, varied significantly ( p < 0.05) compared to the control group after the 10 days of levetiracetam exposure (Table 2 ). Though MCV, MCH, and MCHC values of exposed juvenile C. gariepinus increased significantly ( p < 0.05) from day 5 to 10 in the treatment groups compared to the control, there was a mixed trend in the observed values amongst concentrations and durations. MCV values increased from 37.61 ± 1.2 to 42.94 ± 0.23 fl /cell for control and 0.8 mg/L respectively at the end of the 10 days of exposure. After the 5 days of recovery, MCV levels were still elevated, but only significant ( p < 0.05) at the higher concentrations of 0.6 and 0.8 mg/L.Values for MCH increased from 9.73 ± 2.11 to 11.64 ± 1.51 g/cell. After the 5 days of recovery, MCH levels were still higher in the exposed fish than the control, though not significant at any concentration. MCHC levels increased from 25.19 ± 0.91 to 27.11 ± 0.23 g/dL for control and 0.8 mg/L. After the 5 days of recovery, levels were still significantly ( p < 0.05) elevated for all the concentrations. The mean values of the neutrophils, basophils, eosinophils, and monocytes presented in Table 3 , showed an insignificant variation in the mean values, except for lymphocytes, which was significantly ( p < 0.05) lower in the highest concentration compared to the control, at the end of the exposure period (76.01 ± 0.11, Control ; 67.7 1 ± 0.04, 0.08 mg/L). Table 2 Changes in packed cell volume (PCV), red blood cell count (RBC), haemoglobin concentration (Hb), white blood cell count (WBC), Mean corpuscular volume (MCV), Mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) on 10-days exposure of juvenile C. gariepinus to sub-lethal levels of levetiracetam and 5 days recovery period Parameter Conc. (mg/L) Duration (day) 1 5 10 5-d withdrawal PCV (%) Control 36.00 ± 2.65 a1 34.67 ± 1.53 a1 36.00 ± 3.46 a1 37.33 ± 3.79 a1 0.2 35.00 ± 1.00 a1 32.00 ± 1.00 a1 34.33 ± 2.08 a1 34.00 ± 3.00 b1 0.6 35.33 ± 1.53 a2 27.33 ± 1.53 b1 31.00 ± 2.65 b12 31.00 ± 1.00 c12 0.8 35.67 ± 2.52 a2 28.33 ± 1.53 ab1 26.67 ± 1.53 c1 30.67 ± 2.08 c12 RBC (x10 12 /L) Control 9.64 ± 0.41 a1 9.69 ± 0.22 a1 9.75 ± 0.66 a1 10.13 ± 0.56 a1 0.2 9.44 ± 0.23 a2 7.57 ± 0.33 b1 7.25 ± 0.70 b1 9.20 ± 0.47 a2 0.6 9.52 ± 0.22 a2 6.49 ± 0.34 b1 6.45 ± 0.48 b1 9.03 ± 0.06 a2 0.8 9.55 ± 0.07 a2 6.27 ± 0.13 b1 6.21 ± 0.17 b1 9.30 ± 0.12 a2 Hb (g/dl) Control 9.30 ± 0.26 a1 9.43 ± 0.35 a1 9.07 ± 0.12 a1 9.27 ± 0.31 a1 0.2 9.17 ± 0.12 a3 8.47 ± 0.12 b2 7.27 ± 0.12 b1 9.33 ± 0.25 a3 0.6 9.27 ± 0.12 a3 8.23 ± 0.15 b2 7.13 ± 0.06 b1 9.20 ± 0.17 a3 0.8 9.03 ± 0.06 a2 7.63 ± 0.49 b1 7.23 ± 0.21 b1 9.47 ± 0.12 a2 WBC (x10 6 /L) Control 8467 ± 306 a1 8400 ± 2.65 a1 8467 ± 493 a1 8433 ± 153 a1 0.2 8567 ± 351 a2 8200 ± 361 b 8150 ± 100 b3 8269 ± 321 b2 0.6 8267 ± 153 a2 8700 ± 100 c3 8254 ± 872 b3 8298 ± 321 b2 0.8 8567 ± 351 a2 8367 ± 153 c3 7383 ± 252 c4 7847 ± 208 c3 MCV (fl/cell) Control 37.34 ± 2.61 a1 35.78 ± .22a1 37.61 ± 1.2 1a1 36.85 ± 1.22 a1 0.2 37.07 ± 1.88 a1 42.27 ± 1.31 b2 47.35 ± 1.11 b3 36.95 ± 0.58 a1 0.6 37.11 ± 2.21 a1 42.11 ± .91 b2 48.6 ± 2.11 b3 34.33 ± 1.52 b4 0.8 37.35 ± 3.22 a1 45.18 ± 1.1 c2 42.94 ± 0.23 c2 33.00 ± 0.34 b3 MCH (pg/cell) Control 9.65 ± 4.53 a1 9.73 ± 2.11 a1 9.30 ± 0.21 a1 9.15 ± 1.22 a1 0.2 9.71 ± 1.22 a1 11.23 ± 0.21 b1 10.30 ± 1.19 a1 10.14 ± 0.53 a1 0.6 9.74 ± 3.21 a1 12.68 ± 0.22 b2 11.50 ± 1.43 b2 10.19 ± 1.22 a2 0.8 9.46 ± 2.22 a1 12.17 ± 0.32 b2 11.64 ± 1.51 b2 10.18 ± 1.24 a2 MCHC(g/dL) Control 25.83 ± 2.11 a1 27.20 ± 1.41 a1 25.19 ± 0.91 a1 24.83 ± 1.09 a1 0.2 26.20 ± 3.11 a1 26.50 ± 0.02 a1 26.17 ± 0.21 b1 27.44 ± 0.65 b1 0.6 26.24 ± 1.21 a1 30.11 ± 0.11 b2 23.00 ± 1.21 c3 29.68 ± 1.15 c2 0.8 24.63 ± 2.1 a1 26.93 ± 0.05 a2 27.11 ± 0.23 b2 30.88 ± 0.45 c3 NB: Values with different lower - case alphabets superscripts between different drug concentrations along a column were significantly different, while values with different numeric superscripts across a row were significantly different (p < 0.05). Table 3 Neutrophils, Lymphocytes, Monocytes, eosinophils and basophils counts of juvenile C. gariepinus on 10-day exposure to and 5-day withdrawal from Levetiracetam Parameter Conc. (mg/l) Duration (day) 1 5 10 5-d withdrawal Neutrophils (%) Control 21.60 ± 0.22 a1 21.70 ± 0.26 a1 21.00 ± 0.56 a1 21.03 ± 0.11 a1 0.2 20.00 ± 0.18 a1 22.40 ± 0.27 a1 26.25 ± 1.22 a1 23.22 ± 0.24 a1 0.6 22.60 ± 0.21 a1 23.60 ± 0.45 a1 23.42 ± 1.08 a1 22.09 ± 0.27 a1 0.8 24.08 ± 1.00 a1 24.01 ± 0.62 a1 27.63 ± 1.22 a1 27.24 ± 1.01 a1 Lymphocytes (%) Control 75.22 ± 0.62 a1 75.12 ± 0.81 a1 76.01 ± 0.21 a1 76.01 ± 0.11 a1 0.2 77.25 ± 0.48 a1 75.02 ± 0.21 a1 69.02 ± 0.22 b1 72 .22 ± 0.24 a1 0.6 75.22 ± 0.91 a1 74.13 ± 0.55 a1 75.31 ± 0.42 a1 75 .21 ± 0.34 a1 0.8 75.24 ± 0.83 a1 75.87 ± 0.28 a1 67.21 ± 1.2 b 2 67.7 1 ± 0.04 b2 Monocytes (%) Control 1.33 ± 0.58 a1 1.35 ± 1.00 a1 1.97 ± 1.00 a1 1.26 ± 1.00 a1 0.2 1.00 ± 1.00 a1 0.67 ± 0.58 a1 2.33 ± 1.53 a1 1.00 ± 1.00 a1 0.6 2.00 ± 1.00 a1 1.67 ± 1.15 a1 1.33 ± 1.53 a1 1.67 ± 1.15 a1 0.8 1.67 ± 0.58 a1 1.33 ± 1.15 a1 2.33 ± 0.58 a1 3.00 ± 1.00 a1 Eosinophils (%) Control 1.33 ± 1.15 a1 1.00 ± 1.00 a1 0.67 ± 0.58 a1 1.00 ± 0.00 a1 0.2 0.33 ± 0.58 a1 0.33 ± 0.58 a1 1.00 ± 0.00 a1 0.00 ± 0.00 a1 0.6 1.00 ± 1.00 a1 1.00 ± 0.00 a1 0.67 ± 0.58 a1 0.33 ± 0.58 a1 0.8 1.33 ± 0.58 a1 0.67 ± 0.58 a1 1.00 ± 0.00 a1 1.33 ± 0.58 a1 Basophils (%) Control 0.33 ± 0.58 a1 1.00 ± 1.00 a1 0.33 ± 0.58 a1 0.67 ± 0.58 a1 0.2 0.00 ± 0.00 a1 0.33 ± 0.58 a1 0.00 ± 0.00 a1 0.33 ± 0.58 a1 0.6 0.33 ± 0.58 a1 0.67 ± 0.58 a1 0.33 ± 0.58 a1 0.33 ± 0.58 a1 0.8 0.00 ± 0.00 a1 0.00 ± 0.00 a1 0.33 ± 0.58 a1 0.67 ± 0.58 a1 NB: Values with different lower - case alphabets superscripts between different drug concentrations along a column were significantly different; while values with different numeric superscripts across a row were significantly different (p < 0.05). 3.3 Effects of Levetiracetam on Blood Serum Biochemical Parameters of C. gariepinus Levetiracetam elicited a concentration- and duration-dependent significant (p < 0.05) increase in Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline phosphatase (ALP) in exposed C. gariepinus compared to the control (Table 4 ). Blood serum AST, ALT and ALP activities were highest on the 10th day of treatment and at the highest drug concentrate 0.8 mg/L. AST levels increased from 22.67 ± 2.52 to 49.67 ± 2.08 U/L for the control and 0.8 mg/L respectively, at the end of the 10 days of exposure. Within the same time frame, ALT and ALP activities rose from 31.67 ± 3.21 to 67.67 ± 3.51 U/L and 47.33 ± 4.16 to 85.67 ± 3.06 U/L for control and 0.8 mg/dL respectively. After the 5 days recovery period,AST, ALT and ALP activities remained significantly (p < 0.05) higher than the control. The values for blood serum glucose and protein decreased significantly (p < 0.05) in a dose- and duration- dependant pattern compared to the control (Table 4 ). Protein levels decreased from 79.33 ± 3.77(Control) to 68.51 ± 2.48 mg/dL (0.8 mg/L) at the end of the 10 days exposure period, while glucose decreased from 6.84 ± 0.78 to 5.15 ± 0.76 mg/dL for control and 0.8 mg/dL respectively. At the end of the 5-days recovery period, the values for protein in the exposed fish, were significantly (p < 0.05) lower than those of the control at all the concentration levels, while for glucose, values were only significantly different (p < 0.05) for the fish exposed to 0.8 mg/L, when compared to the control. Table 4 Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline phosphatase (ALP) of juvenile C. gariepinus on 10-day exposure to and 5-day withdrawal from levetiracetam Parameters Conc. (mg/l) Duration (day) 1 5 10 5-d withdrawal AST(U/L) Control 24.00 ± 2.00 a1 22.67 ± 3.79 b1 22.67 ± 2.52 b1 24.33 ± 2.52 b1 0.2 23.67 ± 2.08 a1 26.67 ± 1.15 a1 45.00 ± 2.00 a3 32.00 ± 2.00 a2 0.6 22.67 ± 2.52 a1 30.67 ± 1.53 a2 45.33 ± 1.15 a3 32.00 ± 2.00 a2 0.8 24.33 ± 1.15 a1 33.67 ± 3.52 a2 49.67 ± 2.08 a3 30.33 ± 1.53 a12 ALT (U/L) Control 35.00 ± 1.00 a1 35.00 ± 2.65 b1 31.67 ± 3.21 b1 32.00 ± 2.00 b1 0.2 36.00 ± 2.00 a1 47.00 ± 2.65 a2 61.67 ± 2.08 a3 46.33 ± 5.03 a12 0.6 35.67 ± 2.08 a1 50.33 ± 1.53 a2 66.00 ± 1.00 a3 47.00 ± 4.36 a12 0.8 38.33 ± 1.53 a1 57.00 ± 2.65 a2 67.67 ± 3.51 a3 44.00 ± 2.65 a1 ALP ( U/L) Control 51.33 ± 3.06 a1 51.67 ± 5.51 b1 47.33 ± 6.66 b1 47.33 ± 4.16 b1 0.2 51.67 ± 4.16 a1 73.67 ± 3.51 a2 89.67 ± 5.03 a3 80.33 ± 3.21 a3 0.6 52.00 ± 1.00 a1 79.33 ± 2.52 a2 92.00 ± 2.00 a3 85.00 ± 1.00 a2 0.8 51.00 ± 2.65 a1 84.67 ± 4.16 a2 96.33 ± 2.08 a3 85.67 ± 3.06 a2 Glucose (mg/dL) Control 65.01 ± 2.21 a1 73.22 ± 2.16. a1 79.33 ± 2.22 a1 79.33 ± 3.77 a1 0.2 65.08 ±. 2.43 a1 50.43 ± 2.06 b1 41.56 ± 2.45 b2 63.54 ± 2.66 b1 0.6 64.13 ± 2.23 a1 52.56 ± 2.08 b1 48.54 ± 2.65 b2 62.52± 2.65 b1 0.8 70.09 ± 2.11 a1 45.32 ± 2.11 b2 43.34 ± 3.2 b2 68.51 ± 2.48 b1 Protein (mg/dL) Control 7.18 ± 2.64 a1 7.65 ± 0.85 a1 7.23 ± 5.44 a1 6.84 ± 0.78 a1 0.2 7.03 ± 2.41 a1 4.64 ± 0.43 b2 5.58 ± 6.31 c3 6.57 ± 0.43 a1 0.6 7.06 ± 2.54 a1 5.02 ± 0.67 b2 4.65 ± 5.32 b2 6.54 ± 0.86 a1 0.8 7.71 ± 2.64 a1 5.25 ± 0.76 b2 4.53 ± 5.76 b3 5.15 ± 0.76 b2 NB: Values with different lower - case alphabets superscripts between different drug concentrations along a column were significantly different; while values with different numeric superscripts across a row were significantly different (p < 0.05). 3.4 Effects of Levetiracetam on oxidative stress and lipid peroxidation indicators of juvenile C. gariepinus The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) oxidative stress indicators, on the liver of exposed juvenile C. gariepinus , were significantly (p ≤ 0.05) inhibited by levetiracetam from day 5 of exposure, compared to the control (Table 5 ). At the end of the 10 days exposure period, values reduced from 6.16 ± 0.29 to 2.84 ± 0.26, 0.67 ± 0.10 to 0.26 ± 0.06 and 8.72 ± 0.48 to 5.07 ± 0.49 IU/L for control and 0.8mg/L concentration exposed fish, for SOD, CAT, and GPx enzymes respectively. After the 5 days of recovery period, SOD, CAT, and GPx enzymes activity levels of exposed fish, returned to pre-exposure levels, and there was no significant difference (p ≥ 0.05) in their activities, when compared to the control (Table 5 ).The increase in MDA activity, an indication of lipid peroxidation was significantly (p ≤ 0.05) dose- and duration- dependent, when compared to the control. MDA values increased from 3.5 to 9.5 mg/dL for control and 0.8 mg/dL exposed fish respectively. At the end of the 5 days recovery period, MDA production remained significantly (p ≤ 0.05) high in all three drug concentrations (Fig. 1 ). Table 5 Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx) and activity in juvenile C. gariepinus on 10-day exposure to and 5-day withdrawal from levetiracetam Parameters Conc. (mg/l) Duration (day) 1 5 10 5-d withdrawal SOD (IU/L) Control 5.65 ± 0.40 a1 5.93 ± 0.07 a1 6.16 ± 0.29 a1 6.04 ± 0.37 a1 0.2 5.78 ± 0.32 a2 3.70 ± 0.07 b1 2.71 ± 0.48 b1 5.31 ± 0.76 a2 0.6 5.88 ± 0.44 a2 3.07 ± 0.78 b1 2.99 ± 0.17 b1 5.59 ± 0.25 a2 0.8 5.57 ± 0.28 a2 3.05 ± 0.75 b1 2.84 ± 0.26 b1 5.43 ± 0.26 a2 CAT (IU/L) Control 0.55 ± 0.02 a1 0.60 ± 0.04 a1 0.67 ± 0.10 a1 0.67 ± 0.07 a1 0.2 0.56 ± 0.03 a3 0.41 ± 0.02 b2 0.28 ± 0.10 b1 0.54 ± 0.08 a3 0.6 0.57 ± 0.02 a2 0.30 ± 0.02 b1 0.23 ± 0.01 b1 0.57 ± 0.03 a2 0.8 0.60 ± 0.08 a2 0.26 ± 0.03 b1 0.26 ± 0.06 b1 0.54 ± 0.10 a2 GPx (IU/L) Control 8.56 ± 0.28 a1 8.27 ± 0.14 a1 8.72 ± 0.48 a1 8.65 ± 0.51 a1 0.2 8.52 ± 0.17 a2 5.31 ± 0.34 b1 6.08 ± 0.35 b1 8.86 ± 0.59 a2 0.6 8.70 ± 0.21 a2 5.06 ± 0.35 b1 4.92 ± 0.41 b1 9.30 ± 0.48 a2 0.8 8.27 ± 0.12 a2 4.24 ± 0.07 b1 5.07 ± 0.49 b1 8.80 ± 0.55 a2 NB: Values with different lower - case alphabets superscripts between different drug concentrations along a column were significantly different; while values with different numeric superscripts across a row were significantly different (p < 0.05). 3.5 Effect of Levetiracetam on the Brain Tissue Acetylcholine (AChE) of juvenile C. gariepinus Acetylcholinesterase activity significantly (p ≤ 0.05) increased from exposure of fish to levetiracetam compared to the control, and values remained significantly (p ≤ 0.05) higher than those of the control after the 5 days post-exposure period (Fig. 2 ). 3.6 Changes in morphological parameters Changes in CF and HIS in the fish exposed to levetiracetam are shown in Table 6 . Though there were concentration- and duration-dependent variations in the CF, they were not significantly different (p > 0.05). A significant ( p < 0.05) increase in HIS occurred on the 10th day in fish exposed to higher concentrations compared to the control, with the highest for 0.8 mg/L of levetiracetam (1.69 ± 0.08 to 1.94 ± 0.18 for control and 0.8 mg/L respectively). Table 6 Changes in correction Factor (CF) and Hepatosomatic indices (HIS) of juvenile C. gariepinus on 10-day exposure to levetiracetam Parameters Conc. (mg/L LEV.) Duration (day) 1 5 10 5-d withdrawal CF Control 0.58 ± 0.03 a1 0.69± 0.04 a1 0.62 ± 0.04 a1 0.53 ± 0.04 a1 0.2 0.72 ± 0.13 a1 0.81 ± 0.14 a1 0.61 ± 0.08 a1 0.54 ± 0.07 a1 0.6 0.74 ± 0.23 a1 0.72 ± 0.06 a1 0.73 ± 0.04 a1 0.52 ± 0.05 a1 0.8 0.71 ± 0.15 a1 0.67 ± 0.57 a1 0.62 ± 0.04 a1 0.51 ± 0.03 a1 HIS Control 1.52 ± 0.02 a1 1.68 ± 0.12 a1 1.69 ± 0.08 a1 1.82 ± 0.05 a1 0.2 1.28 ± 0.12 a1 1.65 ± 0.05 a1 1.45 ± 0.06 a1 1.81 ± 0.06 a1 0.6 1.53 ± 0.23 a1 1.65 ± 0.08 a1 1.81 ± 0.05 b2 1.72 ± 0.02 a1 0.8 1.81 ± 0.04 a1 1.64 ± 0.03 a1 1.94 ± 0.18 b2 1.70 ± 0.03 a1 NB: Values with different lower-case alphabets superscripts between different drug concentrations along a column were significantly different; while values with different numeric superscripts across a row were significantly different (p < 0.05). 4. 0 Discussions In this study, C. gariepinus exposed to levetiracetam manifested various behavioural and stress-related symptoms, such as restlessness (including gasping for air), increased mucus secretion, jerky swimming movement, and loss of equilibrium, at higher concentrations. Similar behavioural and stress-related symptoms were observed in fish exposed to antiepileptic and psychosis drugs such as in C. gariepinus exposed to chlorpromazine (Atama et al. 2020 ; Okpe et al. 2023 ), Carassius auratus exposed to chlorpromazine (Li et al. 2008 )d gariepinus exposed to diazepam (Ogueji et al. 2017b ). Other non-antiepileptic pharmaceuticals that elicited similar behavioural changes in fish were chloramphenicol on C. gariepinus (Nwani et al. 2013a ) and tramadol on Danio rerio (zebrafish) (Bachour et al. 2020 ). Organophosphorus chemicals also elicited similar behavioural responses in C. gariepinus (Edeh et al. 2023 ), Tilapia zilli (Nwani et al. 2013b ) and zebrafish (Koenig et al. 2020 ). The similarities in the behavioural responses of C. gariepinus and other fish to pharmaceuticals and organophosphorus pesticides, suggest common mechanisms of toxicity and cellular responses. Studies have shown that the highest concentration of antipsychotic drugs is found in the brain for exposed fish, followed by the plasma, and liver and the lowest in the muscle (Huerta et al., 2016 ), indicating that the activities of the drugs are optimal in the fish brain. The behavioural changes observed may be brain function related, especially neurotransmission in fish. Levetiracetam may have a neurotoxic effect on the fish, thus affecting the normal function of the nerves (Miron et al. 2005 ; Hamed et al. 2022 ). In addition to neurotoxicity, Gamma-aminobutyric acid (GABA) receptors have also been implicated in the behavioural changes in antiepileptic drug-treated fish. GABA is a nonprotein amino acid inhibitory neurotransmitter,that occurs naturally in microorganisms, plants, and animals (Sarasa et al. 2020 ). It reduces neuronal excitability by inhibiting nerve transmission receptors in fish brains and so has a calming effect (Allen et al. 2023 ). Some antiepileptic drugs are known to bind GABA, reducing its calming effect and inducing high excitability in the fish, which may manifest in behavioural changes such as erratic movement, jerky swimming, and loss of equilibrium (Gupta et al. 2014 ). GABA inhibits the activity of signal-receiving neurons by interacting with the GABA A receptors on these cells. GABA-inhibiting drugs include bicuculline, securinine, metrazol and benzodiazepine. Though levetiracetam does not affect GABA directly, studies have shown that levetiracetam promotes inhibition by reducing the negative allosteric effects of Beta carbolines on GABA A receptors (Rigo et al. 2002 ). Beta-carbolin is naturally occurring and influences brain function, but also exhibits antioxidant effects. It is safe to infer that the causes of behavioural alterations in C. gariepinus from exposure to levetiracetam are mainly neurotoxicity and GABA A receptor inhibition. Exposure of zebrafish to diazepine a GABA A receptors-enhancing drug (Campo-Soria et al. 2006 ), has an anxiolytic effect on the fish, thus confirming that fish are sensitive to GABA modulation and supports the hypothesis that exposure to antipsychotic drugs may lead to a mode of action – mediated effect in fish as it does in humans (Huerta et al. 2016 ). This postulate of mode of action–mediated effect on fish by antiepileptic drugs may also apply to levetiracetam. Levetiracetam has anxiogenic properties and thus exerts anxiolytic effects on humans (Werry and Aman 2013 ). In this study, the fish in the treated aquaria at 0.6 and 0.8 mg/L on the 10th day, suppressed preference for the edge of the experimental tank, while the fish in the control showed a preference for the edge of the tanks. This behaviour observed in C. gariepinus may be an anxiolytic reaction, elicited by the anxiogenic properties of levetiracetam. A similar anxiolytic effect was observed in zebrafish ( Bencan et al. 2009 ) and it was attributed to long treatment and high drug concentration regimen. The alteration in behaviour can either enhance or limit the chances of survival of a fish in the wild. For instance, the decreased activity observed in this study, could affect the ability of the fish to forage, migrate, and avoid natural enemies, as well as their reproductive potential. Increased swimming activity though may aid the fish in escaping from predators and finding refuge in more favourable environments, also predisposes the fish of being preyed upon. However, the extra energy spent on swimming will reduce the condition of the fish and may impair their capacity to face additional stressors. The mucus secretion noted in the skin and gills of fish has a protective function, but the mucus in the gills may also predispose the fish to respiratory impairments as reported by Birlanga et al. ( 2022 ). They further stated that mucus cells contain mucins and polyanions made up of glycoproteins that trap toxicants and bar the entry of toxicants into the gill epithelium. However, the problem associated with the increased mucus cells is an extension in the distance for gas exchange along the secondary lamellae, consequently reducing the efficiency of gas exchange and thereby inducing hypoxic conditions. Blood is an essential medium in assessing the health status of animals. Haematological parameters act as physiological indicators of a changing environment due to their relationship with energy, respiration, and defence mechanisms. In this study, the haematological responses of RBC, Hb, and PCV during exposures to leviteracetam decreased resulting in anemia. Similar results have been reported in C. gariepinus exposed to drugs such as praziquantel (Nwani et al. 2016 ), ivermectin (Ogueji et al. 2019 ) and clotrimazole (Melefa et al. 2020 ). The anaemic effect could be due to levetiracetam toxicity. Hematocrit determined the blood's ratio of plasma to corpuscles and oxygen-carrying capacity. The significant decrease observed in the packed cell volume (PCV) could be attributed to gill damage impaired osmoregulation, and hemodilution due to toxicity. Anaemia impacts on fish growth (Mendez-Martinez et al. 2022). The WBC decreased in all treated fish and during the 5-day withdrawal period compared to the control. Contrary to our findings, increases in WBC were obtained in C. gariepinus exposed to chloramphenicol (Nwani et al. 2013a ), diazepam (Ogueji et al. 2017a ), clotrimazole (Melefa et al. 2020 ). Ajima et al. ( 2017 ) also reported the elevation of WBC in verapamil-exposed Oreochromis niloticus. This low levels of WBC encountered in this study indicates deteriorative effects on the fish immune system with the consequent release of lymphocytes from lymphomyeloid tissues. Low levels of WBC can be caused by medication, chronic stress and infection (Munker 2007 ). The leucocyte differentials in C. gariepinus exposed to levetiracetam were comparable to the control throughout the duration of the experiment, except for the lymphocytes, which were significantly lower than those of the control. This is contrary to the observations recorded in other fishes exposed to different toxicants (Mohammad et al. 2012; Nwani et al. 2016 ). Low lymphocyte levels in humans is caused by infections, medication, nutritional deficiency, liver damage, and inflammatory disorder among others (Witeska et al. 2023). In this study, the lymphocytes were the most abundant of the leucocyte differentials. Leucocyte levels decreased from 75% in the control fish to 67% in the exposed fish. The decrease in lymphocytes were responsible for the low level of WBC registered in this study. There were no significant differences in the values of MCV, MCH and MCHC in exposed fish compared to the control. Similar to our finding, Nwani et al. ( 2013b ) reported no significant difference in MCV, MCH and MCHC values in C. gariepinus exposed to praziquantel. No significant change of MCHC in Onchorrynchus mykiss exposed to carbamazepine was also reported (Li et al. 2011 ). Contrary to our report however, increased MCV, MCH and MCHC values were reported in C. gariepinus exposed to clotrimazole (Melefa et al. 2020 ) and acetylsalicylic acid (Siddeswaran et al. 2020 ). The toxicity tests showed haematological changes, indicating toxicity in the treated fish. The haematological profile of C. gariepinus can be used as a biomarker of distress in response to exposure to the antiepileptic drug levetiracetam. Levetiracetam-related concentration and duration-dependent elevation in activities of AST, ALT and ALP occurred in C. gariepinus . The significant increase in these parameters in the exposed fish may be attributed to the hepatotoxic effects of levetiracetam resulting in inflammation and liver damage (Attilakos et al. 2018 ). Similar results were obtained by other studies, that recorded an increase in AST and ALT in fish exposed to pharmaceuticals (Nwani et al. 2013a ; Ogueji et al. 2017a ; Melefa et al. 2020 ; Odo et al. 2020 ), increased ALP correlates with the findings of Folarin et al. (2019). For all the biochemical indices observed, the 5-day post-exposure recovery period was not enough to revert the damage. This is an indication that the hepatotoxic effect on the fish was far-reaching and other interventions other than repairs induced by the system, may be needed to repair the damage to the fish's liver. Oxidative stress is a phenomenon caused by an imbalance between the production and accumulation of oxygen-reactive species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products using antioxidants (Pizzino et al. 2017 ). Antioxidant enzymes play major roles in preventing cellular damage in animals. Superoxide dismutase SOD, a major enzyme in the antioxidant defense systems acts on the Superoxide anion to avoid accumulation of the highly reactive and deleterious O-² (Biller and Takahashi 2018 ). Catalase (CAT) belongs to the group known as the first line of defense antioxidants because it prevents or suppresses free radical formations in the cells (Ighodaro and Akinloye 2018 ). The CAT catalyzes the decomposition of H 2 O 2 into H 2 O and O 2 , maintaining the balance between ROS formation and elimination (Biller and Takahashi 2018 ).CAT has the function of breaking down hydrogen peroxide, which when in high concentration in the body may lead to complications. Deficiency of catalase is called acatalasemia. GPx neutralizes hydrogen peroxide H 2 O 2 in the presence of glutathione in water to limit its harmful effects (Biller and Takahashi 2018 ). The study also showed a significant decrease in the activities of the antioxidant enzymes Superoxide dismutase (SOD), Catalase (CAT), and Glutathione peroxidase (GPx), while malondialdehyde (MDA) increased significantly, in the liver among the sexposed groups compared to the control. This is similar to the reports of various authors (Vadhva and Hasan 1986 ; Yadav et al. 2015 ; Nwani et al. 2016 ; Ogueji et al. 2017b ). The inhibition of SOD, CAT and GPx activities in the liver tissues predisposed the fish to inflammation and stress due to increased free radicals (Nwani et al. 2016 ), resulting in elevated MDA values in the exposed fish. Assessment of LPO is by the measurement of malondialdehyde (Tsikas 2017 ). MDA is one of the final products of polyunsaturated fatty acids peroxidation in the cells. Elevated MDA indicates an increase in lipid peroxidation which leads to a further increase in the production of reactive oxygen species (ROS). The interaction of ROS with biological molecules may cause DNA damage and protein oxidation, resulting in the disturbance of the physiological process (Ogueji et al. 2017b ). The elimination of hydroperoxides is part of the cellular defense mechanism against oxidative stress and consequently, lipid peroxidation (Van der Oost et al. 2003 ). Elevated MDA is an indicator of enhanced oxidative stress (Buyukokuroglu et al. 2002 ). Lipid peroxidation (LPO) is an indication of oxidative stress which is formed by the attack of unsaturated fatty acids by free radicals (generated during drug metabolism) in biomembranes (Ayala et al. 2014 ). Continuous increase in Lipid peroxidation can lead to modification of cellular function, and cell and organ damage (Ayala et al. 2014 ). It is safe to say that, a decrease in SOD, CAT and GPx, was attributed to direct damage of its protein structure by levetiracetam and increasing amounts of hydrogen peroxide produced. This is an indication that levetiracetam in an aquatic environment, could induce oxidative stress in fish. The reduction of CAT, SOD and GPx further encourages the vulnerability of the lymphoid tissues to oxygen metabolites and acid-mediated cell damage. The continuous oxidative damage caused to the cells could disable them and eventually break down completely the self-defense mechanisms of the cells (Biller and Takahashi 2018 ). Acetylcholinesterase (AChE) plays a crucial role in terminating the action of acetylcholine (ACh), a neurotransmitter involved in neuronal communication. By rapidly hydrolyzing acetylcholine, AChE helps restore the synaptic environment to baseline levels, allowing for proper neuronal signaling (Picciotto et al. 2012 ). Acetylcholinesterase (AChE) activity increased from exposure of fish to levetiracetam. The increase in AChE was significant on day 5 and day 10 of exposure in all three levetiracetam concentrations and day 5 post-exposure period. Similarly, the antipsychotic drug chlorpromazine elevated AChE activities in C. gariepinus (Atama et al. 2020 ). High acetylcholinesterase level is a compensatory mechanism to decrease the high acetylcholine levels. It results in excessive accumulation of acetylcholine at the neuromuscular junctions and synapses causing symptoms of both muscarinic and nicotinic toxicity. These include increased muscular fasciculation and glandular secretions (Tsai and Tsai 2021 ). Acetylcholine is synthesized in the cytosol of nerve terminals and is then stored in synaptic vesicles before exocytotic release. Cholinergic nerve terminals synthesize and release the neurotransmitter acetylcholine. Excessive acetylcholine is known as a cholinergic crisis. High levels of acetylcholine have been reported to be responsible for the restlessness, jerky movement and loss of equilibrium of C. gariepinus. ACh is also involved in the immune system because it is secreted by the T lymphocytes. Low carbamazepine (CBZ), a classical antiepileptic drug elicited increased AchE activities in the zebrafish ( Danio rerio ) brain (Da Silve Santos et al. 2010). Low protein content was reported in the treated fish. This is similar to reports by Melefa et al. ( 2020 ) and Okpe et al. ( 2023 ). Low levels of protein encountered in this study, may be a result of protein oxidation initiated by oxidative stress, produced by the inhibition of antioxidants and elevation of MDA in the treated fish. Protein and glucose are reduced in C. gariepinus treated with chlorpromazine (Okpe et al. 2023 ). Low glucose levels encountered may be a result of increased swimming which demands more energy and subsequent conversion of more glucose to energy. Well-being in fish in an environment can be determined by the condition factor and hepatosomatic indices (HIS). In this study, there was no noticeable response of the condition factor to the exposure of levetiracetam. Similar to our findings, Okpe et al. ( 2023 ) reported that the condition factor in C. gariepinus was not altered when exposed to chlorpromazine. The same was reported when Oncorhynchus mykiss was exposed to carbamazepine (Odo et al. 2020 ). Levetiracetam has no significant effect on the ratio of length to weight of the fish. Similar changes were reported in the hepatosomatic index of fish from the influence of pharmaceuticals (Odo et al. 2020 ) and other xenobiotics (Segner et al. 2021 ). HIS values were elevated in C. gariepinus exposed to levetiracetam. This elevation was significant at 0.6 and 0.8 mg/L on the 10th day of the exposure. 4.1 Conclusion The study showed that levetiracetam is toxic to C. gariepinus . It caused significant alterations in fish behaviour, haematological, serum biochemical and liver antioxidant enzyme profiles at various sub-lethal levels. It decreased the values of Hb, PCV, RBC, and WBC, while MCH, MCV, MCHC, and white blood differentials were the same as the control. Serum biochemical profile AST, ALP, and ALT were elevated indicating that levetiracetam induced damage to liver tissues. Glucose and protein decreased significantly. The activities of antioxidant enzymes such as SOD, CAT, and GPx decreased in liver tissues of C. gariepinus exposed to sub-lethal levels of levetiracetam, increasing oxidative stress as indicated in the elevated levels of MDA activity. Elevated activities of AChE in sub-lethal concentrations of levetiracetam are indicative of its effect on brain neurotransmission and its anxiolytic impact on C. gariepinus at high concentrations. The combined use of biochemical and oxidative stress biomarkers using fish models may be useful in the assessment of pharmaceuticals in aquatic ecosystems. Suppression of the urge to take refuge is an anxiolytic and drug mode of action behaviour of C. gariepinus exposed to high concentrations of levetiracetam. Further studies on the toxicokinetic and toxicodynamics of levetiracetam are necessary for greater insight into the mechanisms of action that induced oxidative stress. Declarations Ethical Approval All the animal procedures were performed per the standards outlined in the guidelines for the care and use of experimental animals by the Research Ethical Committee of the University of Nigeria, Nsukka. The proposal of this study was approved by the Research Ethical Committee of the University of Nigeria, before the commencement of the study. Consent to Participate Not applicable to this study. Consent to Publish Not applicable to this study. Authors’ Contributions The conception of the project topic and design was done by Ekenma Julia Agwu, fish procurement and management by Uba Perpetua Ebube and drug procurement and test concentrations by Inwelegbu Valentine Chukwuemeka. Analysis and results were handled by Joy Ihuoma Nzei. First draft of the manuscript was written by Ekenma Julia Agwu, while all the authors edited and approved the manuscript for publication. Funding This article did not receive any form of funding. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4523849","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":398936874,"identity":"909ce74e-bf68-493f-b9ae-636300ab0979","order_by":0,"name":"Joy Ihuoma Nzei","email":"","orcid":"","institution":"University of Nigeria Faculty of Biological Sciences","correspondingAuthor":false,"prefix":"","firstName":"Joy","middleName":"Ihuoma","lastName":"Nzei","suffix":""},{"id":398936875,"identity":"9b18d07a-ecce-47dc-8dd7-17b4e2f6afb8","order_by":1,"name":"Ekenma Julia Agwu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYDACHgST8QGETiBeC7MByVrYJIjSws9z+NijGzUM8vIROWbVvDvuMPCz5xgwF/zCrUWyty3dOOcYg+HGGzlmt3nPPGOQ7HljwDyzD7cWg/M8ZtI5bAyMG2eDtLQdZjC4AbSFtwe3Fvvz/N+kc/4x2IO0FIO02BPSYsDbwyad28aQOF86x4wZbIsEUAvPD9xaJM4cM5PO7ZNI3iD/rFhybtthHokzzwoO8zbg1sLfk/xMOuebje38nsMbP7xtOyzH35688THPH9xaYJYxGByAsMDxdICxjaAWBgZ5VKcQtmUUjIJRMApGDgAA7GBL/G3AECgAAAAASUVORK5CYII=","orcid":"https://orcid.org/0009-0000-7371-730X","institution":"University of Nigeria Faculty of Biological Sciences","correspondingAuthor":true,"prefix":"","firstName":"Ekenma","middleName":"Julia","lastName":"Agwu","suffix":""},{"id":398936876,"identity":"2db19387-c130-4512-9bd5-c924755379dd","order_by":2,"name":"Perpetua Ebube Uba","email":"","orcid":"","institution":"University of Nigeria Faculty of Biological Sciences","correspondingAuthor":false,"prefix":"","firstName":"Perpetua","middleName":"Ebube","lastName":"Uba","suffix":""},{"id":398936877,"identity":"a1850a07-c584-4d94-aa5b-4a8f465e203d","order_by":3,"name":"Inwelegbu Valentine Chukwuemeka","email":"","orcid":"","institution":"University of Nigeria Faculty of Biological Sciences","correspondingAuthor":false,"prefix":"","firstName":"Inwelegbu","middleName":"Valentine","lastName":"Chukwuemeka","suffix":""}],"badges":[],"createdAt":"2024-06-03 19:58:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4523849/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4523849/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11356-025-36281-y","type":"published","date":"2025-03-25T15:56:50+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":73316073,"identity":"76c36bfc-6076-4c4d-86d4-f1e6bfc50152","added_by":"auto","created_at":"2025-01-08 20:00:25","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":75689,"visible":true,"origin":"","legend":"\u003cp\u003eLipid peroxidation in juvenile \u003cem\u003eC. gariepinus\u003c/em\u003e on 10-day exposure to and 5-day withdrawal from levetiracetam. Significant at ****p \u0026lt; 0.0001.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4523849/v1/2f76131ce1699314ddf1f2ab.jpeg"},{"id":73314787,"identity":"38b0c6ed-eb9c-4c1d-964e-b3ff1b39e038","added_by":"auto","created_at":"2025-01-08 19:52:25","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":73887,"visible":true,"origin":"","legend":"\u003cp\u003eAcetylcholinesterase (AChE) activity in juvenile \u003cem\u003eC. gariepinus\u003c/em\u003e on 10-day exposure to and 5-day withdrawal from levetiracetam. Significant at *p \u0026lt; 0.05, ****p \u0026lt; 0.0001.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4523849/v1/f2ec091a045c4dfab22db79d.jpeg"},{"id":79604775,"identity":"54ee15c6-a6b2-4be3-acfb-22592ec828fc","added_by":"auto","created_at":"2025-03-31 16:05:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1894200,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4523849/v1/6d17c928-3eb0-45e5-af6e-52c7bcf28759.pdf"}],"financialInterests":"","formattedTitle":"Effects of Levetiracetam an Antiepileptic Drug on the Multi-biological Parameters in African catfish Clarias gariepinus (Burchell, 1822)","fulltext":[{"header":"1.0 Introduction","content":"\u003cp\u003eThe widespread use of pharmaceuticals and their subsequent release into aquatic ecosystems, has raised concerns about their potential eco-toxicological impact on non-target organisms (Ebele 2020). Levetiracetam, an antiepileptic drug (AED), chemically known as (S)-ethyl-2-oxo-1-pyrrolidineacetamide and an analogue of the neurotransmitter γ-aminobutyric acid (GABA), is commonly used due to its favourable pharmacokinetic profile and low incidence of adverse effects in humans (Cereghino et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2000\u003c/span\u003e). It is also used off-label for the prophylaxis of traumatic brain injury (TBI) and supratentorial neurosurgery (Jones et al. \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2008\u003c/span\u003e). It is not extensively metabolized and has a low potential for drug interactions involving hepatic enzymes. This characteristic makes it a favourable choice for patients taking multiple medications, as it is less likely to interfere with the metabolism of other drugs (Cereghino et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2000\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eLevetiracetam is eliminated through the kidneys, through urine unchanged (Perucca and Bialer \u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e1996\u003c/span\u003e) and can enter water bodies through various channels including human and animal excretion, hospital waste/discharge/effluents, landfills leachates (Bilbao-Meseguer et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) and agricultural runoffs into the ground and surface water and in the aquatic environment, through dilution, degradation, and adsorption can find their way into the tissues of aquatic organisms (Zhu et al. \u003cspan citationid=\"CR98\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), having the potential to impact the aquatic life and beyond.\u003c/p\u003e \u003cp\u003eStudies have shown that some pharmaceuticals, including AEDs are toxic to aquatic organisms including fish. Carbamazepine was harmful to aquatic microalgal species (Haase et al. \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2015\u003c/span\u003e), \u003cem\u003eDaphnia magna\u003c/em\u003e (Oliveira et al. \u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e2015\u003c/span\u003e), \u003cem\u003eCarassius auratus\u003c/em\u003e (Li et al. \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e2008\u003c/span\u003e)d \u003cem\u003egariepinus\u003c/em\u003e (Ogueji et al. \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e2017a\u003c/span\u003e). It has also suppressed steroidogenesis in organisms (Hinfray et al. \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2011\u003c/span\u003e; Wassmur et al. \u003cspan citationid=\"CR90\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Diazepam is toxic to \u003cem\u003eC. clariepinus\u003c/em\u003e (Ogueji et al. \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e2017b\u003c/span\u003e), diclofenac to \u003cem\u003eOreochromis\u003c/em\u003e sp. (Krishnapriya et al. \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2017\u003c/span\u003e), zebrafish (Bio and Nunes \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) and biphenol to Indian major carp \u003cem\u003eLabeo rhita\u003c/em\u003e (Krishnapriya et al. \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Aquatic organisms, including fish, play vital roles in ecosystem dynamics and can serve as indicators of environmental health. Studying the effects of pharmaceuticals on these organisms is crucial to understanding their potential ecological consequences (Klanovicz et al. 2021). Exposure to pharmaceuticals in the aquatic system can cause biological changes in organisms, especially fish. These changes are called biomarkers and are used as indicators of exposure to environmental pollutants. These biomarkers enable the rapid assessment of the health of organisms and warn about possible environmental risks (Van der Oost et al. \u003cspan citationid=\"CR89\" class=\"CitationRef\"\u003e2003\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe presence of levetiracetam in aquatic environments has been detected, and its effects on aquatic organisms, particularly fish species, remain poorly understood (Pier\u0026oacute;g et al. \u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Literature on the toxicological effects of levetiracetam on freshwater fishes is scanty. This is because levetiracetam is a second-generation antiepileptic drug, i.e. it is new in the market (Sabaa et al. \u003cspan citationid=\"CR80\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Suzuki et al. \u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). In Nigeria, no research to the best of our knowledge has been published on the effects of levetiracetam on freshwater fishes in the aquatic ecosystem. The African catfish \u003cem\u003eC. gariepinus\u003c/em\u003e is one the commercial indigenous fish species preferred due to its fast growth, nutritional quality, easy domestication, high reproductive potential and adaptability to extreme water quality conditions (Maranga et al. \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). These qualities make \u003cem\u003eC. gariepinus\u003c/em\u003e highly popular amongst aquaculture farmers and also a vital organism in ecosystem dynamics, as it can serve as an indicator of environmental health. Thus, this study was aimed at investigating the sub-lethal effects of levetiracetam on the behaviour, haematological, biochemical, lipid peroxidation, oxidative stress and biometric parameters of \u003cem\u003eC. gariepinus\u003c/em\u003e and the recovery ability of the fish post-drug exposure.\u003c/p\u003e"},{"header":"2.0 Materials and Methods","content":"\u003cp\u003e \u003cb\u003eFish sampling and management\u003c/b\u003e \u003c/p\u003e \u003cp\u003e\u003cem\u003eC. gariepinus\u003c/em\u003e juveniles (n\u0026thinsp;=\u0026thinsp;306), of mean length 9.01\u0026thinsp;\u0026plusmn;\u0026thinsp;9 cm and weight, 6.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24 g were procured from Freedom Fisheries Limited Farm, Nsukka, Enugu State and were transported to the Zoological Garden of the Department of Zoology and Environmental Biology, University of Nigeria, Nsukka. The fish were kept in 5 plastic bowls (20 litres), containing 10L of filtered de-chlorinated water. During the acclimatization and sub-lethal exposure period, the fish were fed a commercial standard diet of dry pellet feed (Aller Aqua Nigeria limited) at 3% body weight per day, and the water changed every 24 h just before feeding. They were fed daily (8\u0026ndash;10 am).The study was carried out in an indoor experimental system, within normal photoperiod of day/night (14:10) cycle common at Nsukka, Nigeria, and the fish were sustained at temperature of 26.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u0026deg;C, pH of 7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5, and dissolved oxygen of 97% saturation. All the animal procedures were performed per the standards outlined in the guidelines for the care and use of experimental animals by the research ethical committee of the University of Nigeria, Nsukka. The fish were acclimatized for 14 days to laboratory conditions before starting the experiment. All the test procedures adhered to OECD guideline 215 (OECD 2000) and were conducted under conditions similar to acclimation.\u003c/p\u003e \u003cp\u003e \u003cb\u003eTest drug\u003c/b\u003e \u003c/p\u003e \u003cp\u003eCommercial pharmaceutical preparations of the anti-epileptic drug with the trade name Suvitra, containing 500 mg of levetiracetam as the active pharmaceutical ingredient (API) in a tablet (Micro Labs Limited, India) was used. A stock solution of the drug was prepared by dissolving 10 tablets containing 500 mg of levetiracetam (as the active ingredient) each in 10 L of the filtered, dechlorinated water. The stock solution was used in preparing the test solutions with nominal concentrations of levetiracetam.\u003c/p\u003e \u003cp\u003e \u003cb\u003eDesign of experiments for acute exposure and LC\u003c/b\u003e \u003csub\u003e \u003cb\u003e50\u003c/b\u003e \u003c/sub\u003e \u003c/p\u003e \u003cp\u003eA range finding test was carried out, and the appropriate range of levetiracetam concentrations (12.5 and 62.5 mg/L) that can cause percentage mortalities of 0% and 100%, respectively, was selected. From the obtained range values, ten fish each from the acclimatized batch were then exposed to five (12.5, 25.0, 37.5, 50.0, and 62.5 mg/L) nominal concentrations of levetiracetam and distilled water only (0 mg/L), for the control. The experimental setup and control were replicated three times for strong statistical analysis. The fish were not fed during the acute toxicity studies to prevent interference from faeces. The 24, 48, 72, and 96h survival and mortality rates were noted. Forceps were used to remove the dead fish immediately to prevent deterioration of the test media. Before removal of the fish, they were regarded as dead when their operculum stopped beating. The LC\u003csub\u003e50\u003c/sub\u003e at the end of the 96 h experimental duration, was determined by probit analysis (Finney \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e1971\u003c/span\u003e), using SPSS 23.0.\u003c/p\u003e \u003cp\u003e \u003cb\u003eSub-lethal levetiracetam administration\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe 96h median concentration (LC\u003csub\u003e50\u003c/sub\u003e) of levetiracetam was calculated to be 37.54 mg/L, according to the probit analysis. Based on the 96 h LC\u003csub\u003e50\u003c/sub\u003e, three different sub-lethal concentrations (0.2, 0.6 and 0.8 mg/L) were selected for the sub-lethal exposure. A total of 120 acclimated fish were used without regard to sex. The fish were not fed 24 hours before the commencement of the experiment. Three treatment concentrations were used for the experiment namely, 0.2, 0.6, 0.8 mg/L of levetiracetam and non- chlorinated tap water only (control). Ten (10) fish each were placed into 4 (four) fresh glass aquaria (60 \u0026times; 30 \u0026times; 30 cm size), labelled A-D. Aquarium A contained 10 L of non- chlorinated tap water only (control), while B, C and D contained 10 L of 0.8, 0.6 and 0.2 mg/L of levetiracetam, respectively. The experimental arrangement was replicated three times, making it a total of 30 fish and 3 aquaria for each treatment concentration and the control.A plastic plant (place of refuge) was placed in each of the glass aquarium, to test the effect of levetiracetam on fish behavioural response to refuge. The experiment was conducted in a static renewal bioassay system in which the water and levetiracetam were changed daily to maintain constant drug concentration. The set-up lasted for 10 days and another 5 days for recovery. Fish in the treatment groups were transferred to aquaria with only de-chlorinated water The fish were fed a small quantity of feed, approximately 3% of the body weight an hour before changing the water and leviteracetam, to avoid mortality arising from starvation. There were no mortalities during the 15-day exposure period. Observations of the behavioural and stress-related responses and clinical signs of toxicity of \u003cem\u003eC. gariepinus\u003c/em\u003e juveniles exposed to the drug were made at the end of the 10-day treatment and 5-day recovery period. Three (3) fishes from each of the experimental and control groups were removed for sampling at the end of day 1, 5, 10 and 15. Blood was collected, and the fish was sacrificed. The liver and brain tissues were excised, weighed, and washed in ice-cold buffer for all the various treatments and intervals. The minced tissues were rinsed clear of blood with cold isolation buffer and homogenized on ice in a glass Potter-Elvehjem homogenizing vessel with a motor-driven pestle. The isolation buffer contained 100 mM Tris-HCl and pH of 7.20 was adjusted with HCl. The liver was used for the oxidative stress and antioxidant enzymes, while the brain was used for the activities of the acetylcholinesterase.\u003c/p\u003e \u003cp\u003e \u003cb\u003eBlood sample collection\u003c/b\u003e \u003c/p\u003e \u003cp\u003e1.0 ml of blood was collected on each sampling day (days 1, 5, 10, and 15), from the three randomly selected fish from each of the treatment groups and the control by cardiac puncture, using a hypodermic heparinized syringe. Half was transferred to an EDTA container to avoid clotting, and used for the estimation of the haematological parameters, while the remaining half was centrifuged at 10000 g at 4\u0026deg;C for 20 min to separate the plasma which was used for the estimation of biochemical parameters.\u003c/p\u003e \u003cp\u003e \u003cb\u003eHaematological assays\u003c/b\u003e \u003c/p\u003e \u003cp\u003eFollowing blood collection, the haematological parameters including red blood cell (RBC), packed cell volume (PCV) also known as haematocrit, haemoglobin (Hb), white blood cells (WBC), Mean Corpuscular volume (MCV), Mean corpuscular haemoglobin concentration (MCHC) and Mean corpuscular haemoglobin (MCH), and differential white blood counts were assessed. RBC counts were estimated using a Neubauer hemocytometer, as described by Rusia and Sood (\u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e1992\u003c/span\u003e). Briefly, 0.02 mL of blood was pipetted from the blood sample and added to 4 mL of the RBC diluting fluid (Toisson\u0026rsquo;s solution) in a clean test tube to make a 1:200 dilution of the blood sample. The diluted blood sample was loaded onto a Neubauer counting chamber, and all RBCs in the five groups of 16 small squares in the central area of the Neubauer chamber were counted using a light microscope under a high power (40 X) objective. The number of cells counted for each sample was multiplied by 10,000 to obtain the RBC count per microliter of blood. Hematocrit (PCV) was determined using the microhematocrit method of Nwani et al. (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e2013a\u003c/span\u003e), Hb determination was done using the cyanmethemoglobin method by Blaxhall and Daisley (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e1973\u003c/span\u003e), determination of leucocytes was by Rusia and Sood (\u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e1992\u003c/span\u003e). Counting the numbers of different types of leucocytes (neutrophils, monocytes, lymphocytes, eosinophils, and basophils) in the blood smears was identified as described by Anderson (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2003\u003c/span\u003e). The number of each type of leukocyte was calculated as a percentage. Erythrocyte indices, such as MCHC, MCH and MCV, were calculated from the results of RBC count, WBC count, Hb, and PCV (Bain et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2016\u003c/span\u003e) according to standard formulae:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:\\text{M}\\text{C}\\text{V}\\:(\\text{f}\\text{l}/\\text{c}\\text{e}\\text{l}\\text{l})=\\frac{\\text{P}\\text{C}\\text{V}\\:\\left(\\text{\\%}\\right)\\:\\text{X}\\:10}{RBC\\:count\\:in\\:millions/L\\:}$$\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Equb\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equb\" name=\"EquationSource\"\u003e\n$$\\:\\text{M}\\text{C}\\text{H}\\text{C}\\:(\\text{g}/\\text{d}\\text{l})=\\frac{\\text{H}\\text{b}\\:\\left(\\frac{\\text{g}}{\\text{d}\\text{l}}\\right)\\:\\text{X}\\:100}{\\text{P}\\text{C}\\text{V}\\:\\left(\\text{\\%}\\right)\\:}$$\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Equc\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equc\" name=\"EquationSource\"\u003e\n$$\\:\\text{M}\\text{C}\\text{H}\\:(\\text{p}\\text{g}/\\text{c}\\text{e}\\text{l}\\text{l})=\\frac{\\text{H}\\text{b}\\:\\left(\\frac{\\text{g}}{\\text{d}\\text{l}}\\right)\\:\\text{X}\\:10}{RBC\\:count\\:in\\:millions/L\\:}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eBiochemical Indices\u003c/b\u003e \u003c/p\u003e \u003cp\u003eRandox diagnostic kits were used for biochemical tests. The activities of aspartate and alanine aminotransferase, alkaline phosphatase, protein, and glucose levels were assayed by the method of Reitman and Frankel (\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e1957\u003c/span\u003e) as outlined in the Randox kit.\u003c/p\u003e \u003cp\u003e \u003cb\u003eAssay of Oxidative Stress, Antioxidant Enzymes and acetylcholinesterase activity\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe Catalase (CAT) activity was determined according to the method described by Aebi (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e1984\u003c/span\u003e). Superoxide dismutase (SOD) activity was determined by measuring the inhibition of antioxidation of epinephrine at pH 10.02 at 30 \u003csup\u003eo\u003c/sup\u003eC (Arthur and Boyne, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e1985\u003c/span\u003e). The activity of glutathione peroxidase (GPx) was measured by the method of Lawrence and Buck (1976), with the specific activity being determined using the extinction coefficient of 6.22 mM/cm. Malondialdehyde (MDA) an index of lipid peroxidation was determined using the method of Buege and Aust (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e1978\u003c/span\u003e). The acetylcholinesterase activity was determined by the methods of Birman (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e1985\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cb\u003eMorphometric variations\u003c/b\u003e \u003c/p\u003e \u003cp\u003eDuring each sampling period, the standard length and body weight of the fish were determined. The weight of the excised liver previously documented was used. Following the methods of White and Fletcher (\u003cspan citationid=\"CR92\" class=\"CitationRef\"\u003e1985\u003c/span\u003e), the condition factor (CF) and hepatosomatic index (HSI) were calculated as:\u003c/p\u003e \u003cp\u003eCF = (Body weight (g)/Standard length (cm)\u003csup\u003e3\u003c/sup\u003e) x 100\u003c/p\u003e \u003cp\u003eHSI = (Liver weight (g)/Body weight (g)) x 100\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAll data were analysed using one-way analysis of variance (ANOVA) using SPSS (version 22.0) followed by Duncan\u0026rsquo;s multiple range post-hoc test. Differences were considered significant at p\u0026thinsp;\u0026le;\u0026thinsp;0.05. Results were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD).\u003c/p\u003e"},{"header":"3. 0 Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Changes in the behaviour of \u003cem\u003eC. gariepinus\u003c/em\u003e exposed to levetiracetam\u003c/h2\u003e \u003cp\u003eAbnormal behavioural responses such as loss of balance, increased mucus secretion, unprecedented swimming, air gulping, and opercular movement rates were documented in the treated fish. At lower concentrations, swimming and opercula movement rates were faster and slower at high concentrations of 0.8 mg/L. Conversely, air gulping, loss of equilibrium, jerky movement, mucus secretion, and skin discolouration increased at higher concentrations during sublethal exposure of \u003cem\u003eC. gariepinus\u003c/em\u003e to levetiracetam as shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. In addition, at low levels of the drug, the fish were also swimming close to the edge of the tanks, but as concentration increased, they avoided the edge of the tanks (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). After 5 days of recovery, the observed abnormalities reduced greatly, especially for the lower concentrations, but not to the levels of the control.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eChanges in the behaviour of \u003cem\u003eC. gariepinus\u003c/em\u003e after 10 days of exposure to a sub-lethal concentration of levetiracetam and 5- days recovery period\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eExposure duration\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003eLevetiracetam concentration (mg/L)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSkin discoloration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLoss of equilibrium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMucus secretion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSwimming rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJerky swimming movement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003csub\u003e+\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOperculum movement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAir gulping\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAvoiding the edge of the tank\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5-d withdrawal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSkin discoloration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLoss of equilibrium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003csub\u003e+\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMucus secretion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSwimming rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJerky swimming movement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOperculum movement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAir gulping\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAvoiding the edge of the tank\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003eKey: \u0026lsquo;-\u0026rsquo; indicates normal behavior/absent, \u0026lsquo;+\u0026rsquo; mild, \u0026lsquo;++\u0026rsquo; moderate, and \u0026lsquo;+++\u0026rsquo; high\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Haematological changes in C. \u003cem\u003egariepinus\u003c/em\u003e exposed to sub-lethal concentrations of levetiracetam\u003c/h2\u003e \u003cp\u003eThe effects of levetiracetam on the haematological profiles PCV, RBC, Hb, WBC, MCH and MCHC, are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Levetiracetam significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) decreased PCV, RBC, WBC and Hb values of the treated fish in a concentration - and duration - dependent manner compared to the control. There was a concentration-dependent decrease in the PCV in \u003cem\u003eC. gariepinus\u003c/em\u003e exposed to levetiracetam form day 5 to 10, but only in the higher concentrations 0.6 and 0.8 mg/L. At the end of the 10 - days exposure period, PCV values ranged from 36.00\u0026thinsp;\u0026plusmn;\u0026thinsp;3.46 to 26.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53% for the control and 0.8 mg/L concentration exposed fis respectively. After the 5- day recovery period, the PCV was still significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) decreased in the treated fish. The RBC counts significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) decreased in a concentration - and duration - dependent manner from day 5 to 10 for the fish exposed to all concentrations. RBC values ranged from 9.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06 to 6.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17 x10\u003csup\u003e12\u003c/sup\u003e /L for the control fish and the .0.8 mg/L exposed fish respectively. The pattern encountered for RBC counts of treated fish, was observed for Hb and WBC. Hb values of the fish decreased from 9.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12 to 7.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21 g/dL, while those for WBC decreased from 8467\u0026thinsp;\u0026plusmn;\u0026thinsp;493 to 7383\u0026thinsp;\u0026plusmn;\u0026thinsp;252 x10\u003csup\u003e6\u003c/sup\u003e/L for the control and 0.8 mg/L exposed fish respectively, at the end of the 10 days exposure period. After 5 days of recovery, RBC, Hb and WBC levels in the fish exposed to various concentrations of the drug, were still reduced when compared to the control. This observed reduction was only significant (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) for WBC and at all concentrations. The results of the erythrocyte indices (MCH, MCV and MCHC) of the treated fish, varied significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) compared to the control group after the 10 days of levetiracetam exposure (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Though MCV, MCH, and MCHC values of exposed juvenile \u003cem\u003eC. gariepinus\u003c/em\u003e increased significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) from day 5 to 10 in the treatment groups compared to the control, there was a mixed trend in the observed values amongst concentrations and durations. MCV values increased from 37.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2 to 42.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23 fl /cell for control and 0.8 mg/L respectively at the end of the 10 days of exposure. After the 5 days of recovery, MCV levels were still elevated, but only significant (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) at the higher concentrations of 0.6 and 0.8 mg/L.Values for MCH increased from 9.73\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11 to 11.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.51 g/cell. After the 5 days of recovery, MCH levels were still higher in the exposed fish than the control, though not significant at any concentration. MCHC levels increased from 25.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.91 to 27.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23 g/dL for control and 0.8 mg/L. After the 5 days of recovery, levels were still significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) elevated for all the concentrations.\u003c/p\u003e \u003cp\u003eThe mean values of the neutrophils, basophils, eosinophils, and monocytes presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, showed an insignificant variation in the mean values, except for lymphocytes, which was significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) lower in the highest concentration compared to the control, at the end of the exposure period (76.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11, Control ; 67.7 1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04, 0.08 mg/L).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eChanges in packed cell volume (PCV), red blood cell count (RBC), haemoglobin concentration (Hb), white blood cell count (WBC), Mean corpuscular volume (MCV), Mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) on 10-days exposure of juvenile \u003cem\u003eC. gariepinus\u003c/em\u003e to sub-lethal levels of levetiracetam and 5 days recovery period\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eConc. (mg/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eDuration (day)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5-d withdrawal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCV (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.65\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36.00\u0026thinsp;\u0026plusmn;\u0026thinsp;3.46\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e37.33\u0026thinsp;\u0026plusmn;\u0026thinsp;3.79\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.08\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34.00\u0026thinsp;\u0026plusmn;\u0026thinsp;3.00\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.65\u003csup\u003eb12\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e31.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003csup\u003ec12\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.52\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003csup\u003eab1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003csup\u003ec1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.08\u003csup\u003ec12\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRBC (x10\u003csup\u003e12\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.56\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.48\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHb (g/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (x10\u003csup\u003e6\u003c/sup\u003e/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8467\u0026thinsp;\u0026plusmn;\u0026thinsp;306\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8400\u0026thinsp;\u0026plusmn;\u0026thinsp;2.65\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8467\u0026thinsp;\u0026plusmn;\u0026thinsp;493\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8433\u0026thinsp;\u0026plusmn;\u0026thinsp;153\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8567\u0026thinsp;\u0026plusmn;\u0026thinsp;351\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8200\u0026thinsp;\u0026plusmn;\u0026thinsp;361\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8150\u0026thinsp;\u0026plusmn;\u0026thinsp;100\u003csup\u003eb3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8269\u0026thinsp;\u0026plusmn;\u0026thinsp;321\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8267\u0026thinsp;\u0026plusmn;\u0026thinsp;153\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8700\u0026thinsp;\u0026plusmn;\u0026thinsp;100\u003csup\u003ec3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8254\u0026thinsp;\u0026plusmn;\u0026thinsp;872\u003csup\u003eb3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8298\u0026thinsp;\u0026plusmn;\u0026thinsp;321\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8567\u0026thinsp;\u0026plusmn;\u0026thinsp;351\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8367\u0026thinsp;\u0026plusmn;\u0026thinsp;153\u003csup\u003ec3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7383\u0026thinsp;\u0026plusmn;\u0026thinsp;252\u003csup\u003ec4\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7847\u0026thinsp;\u0026plusmn;\u0026thinsp;208\u003csup\u003ec3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCV (fl/cell)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.34\u0026thinsp;\u0026plusmn;\u0026thinsp;2.61\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.78\u0026thinsp;\u0026plusmn;\u0026thinsp;.22a1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003csup\u003e1a1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e36.85\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.07\u0026thinsp;\u0026plusmn;\u0026thinsp;1.88\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42.27\u0026thinsp;\u0026plusmn;\u0026thinsp;1.31\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e47.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.11\u003csup\u003eb3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e36.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.11\u0026thinsp;\u0026plusmn;\u0026thinsp;2.21\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42.11\u0026thinsp;\u0026plusmn;\u0026thinsp;.91\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11\u003csup\u003eb3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.52\u003csup\u003eb4\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.35\u0026thinsp;\u0026plusmn;\u0026thinsp;3.22\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45.18\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003csup\u003ec2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003csup\u003ec2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003csup\u003eb3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCH (pg/cell)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.65\u0026thinsp;\u0026plusmn;\u0026thinsp;4.53\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.73\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.15\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.71\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.30\u0026thinsp;\u0026plusmn;\u0026thinsp;1.19\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.74\u0026thinsp;\u0026plusmn;\u0026thinsp;3.21\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.50\u0026thinsp;\u0026plusmn;\u0026thinsp;1.43\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.46\u0026thinsp;\u0026plusmn;\u0026thinsp;2.22\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.51\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.18\u0026thinsp;\u0026plusmn;\u0026thinsp;1.24\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCHC(g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.83\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.20\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.91\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24.83\u0026thinsp;\u0026plusmn;\u0026thinsp;1.09\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.20\u0026thinsp;\u0026plusmn;\u0026thinsp;3.11\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.65\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.24\u0026thinsp;\u0026plusmn;\u0026thinsp;1.21\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.21\u003csup\u003ec3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29.68\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003csup\u003ec2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.63\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30.88\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45\u003csup\u003ec3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNB: Values with different lower - case alphabets superscripts between different drug concentrations along a column were significantly different, while values with different numeric superscripts across a row were significantly different (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNeutrophils, Lymphocytes, Monocytes, eosinophils and basophils counts of juvenile \u003cem\u003eC. gariepinus\u003c/em\u003e on 10-day exposure to and 5-day withdrawal from Levetiracetam\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eConc. (mg/l)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eDuration (day)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5-d withdrawal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophils (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.56 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.25\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.42\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27.24\u0026thinsp;\u0026plusmn;\u0026thinsp;1.01 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e76.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.48 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e69.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22 \u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e72 .22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.91 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e75.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75 .21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67.21\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003csup\u003eb 2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e67.7 1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonocytes (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.97\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.26\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEosinophils (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBasophils (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNB: Values with different lower - case alphabets superscripts between different drug concentrations along a column were significantly different; while values with different numeric superscripts across a row were significantly different (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Effects of Levetiracetam on Blood Serum Biochemical Parameters of \u003cem\u003eC. gariepinus\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eLevetiracetam elicited a concentration- and duration-dependent significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) increase in Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline phosphatase (ALP) in exposed \u003cem\u003eC. gariepinus\u003c/em\u003e compared to the control (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Blood serum AST, ALT and ALP activities were highest on the 10th day of treatment and at the highest drug concentrate 0.8 mg/L. AST levels increased from 22.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.52 to 49.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.08 U/L for the control and 0.8 mg/L respectively, at the end of the 10 days of exposure. Within the same time frame, ALT and ALP activities rose from 31.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.21 to 67.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.51 U/L and 47.33\u0026thinsp;\u0026plusmn;\u0026thinsp;4.16 to 85.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.06 U/L for control and 0.8 mg/dL respectively. After the 5 days recovery period,AST, ALT and ALP activities remained significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) higher than the control. The values for blood serum glucose and protein decreased significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in a dose- and duration- dependant pattern compared to the control (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Protein levels decreased from 79.33\u0026thinsp;\u0026plusmn;\u0026thinsp;3.77(Control) to 68.51\u0026thinsp;\u0026plusmn;\u0026thinsp;2.48 mg/dL (0.8 mg/L) at the end of the 10 days exposure period, while glucose decreased from 6.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78 to 5.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76 mg/dL for control and 0.8 mg/dL respectively. At the end of the 5-days recovery period, the values for protein in the exposed fish, were significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) lower than those of the control at all the concentration levels, while for glucose, values were only significantly different (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) for the fish exposed to 0.8 mg/L, when compared to the control.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline phosphatase (ALP) of juvenile \u003cem\u003eC. gariepinus\u003c/em\u003e on 10-day exposure to and 5-day withdrawal from levetiracetam\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eConc. (mg/l)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eDuration (day)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5-d withdrawal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST(U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.00\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.79\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.52\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.52\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.08\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.00\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.00\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.52\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.00\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.52\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.08\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003csup\u003ea12\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.65\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.21\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.00\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.00\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.65\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e61.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.08\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e46.33\u0026thinsp;\u0026plusmn;\u0026thinsp;5.03\u003csup\u003ea12\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.08\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e66.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47.00\u0026thinsp;\u0026plusmn;\u0026thinsp;4.36\u003csup\u003ea12\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.65\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.51\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e44.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.65\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALP ( U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.33\u0026thinsp;\u0026plusmn;\u0026thinsp;3.06\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51.67\u0026thinsp;\u0026plusmn;\u0026thinsp;5.51\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e47.33\u0026thinsp;\u0026plusmn;\u0026thinsp;6.66\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47.33\u0026thinsp;\u0026plusmn;\u0026thinsp;4.16\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.67\u0026thinsp;\u0026plusmn;\u0026thinsp;4.16\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.51\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e89.67\u0026thinsp;\u0026plusmn;\u0026thinsp;5.03\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e80.33\u0026thinsp;\u0026plusmn;\u0026thinsp;3.21\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.52\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e92.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.00\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e85.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.65\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84.67\u0026thinsp;\u0026plusmn;\u0026thinsp;4.16\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e96.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.08\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e85.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.06\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucose (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.01\u0026thinsp;\u0026plusmn;\u0026thinsp;2.21 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73.22\u0026thinsp;\u0026plusmn;\u0026thinsp;2.16. \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e79.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.22 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e79.33\u0026thinsp;\u0026plusmn;\u0026thinsp;3.77 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.08 \u0026plusmn;. 2.43 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50.43\u0026thinsp;\u0026plusmn;\u0026thinsp;2.06\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41.56\u0026thinsp;\u0026plusmn;\u0026thinsp;2.45\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e63.54\u0026thinsp;\u0026plusmn;\u0026thinsp;2.66\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.13\u0026thinsp;\u0026plusmn;\u0026thinsp;2.23 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52.56\u0026thinsp;\u0026plusmn;\u0026thinsp;2.08\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48.54\u0026thinsp;\u0026plusmn;\u0026thinsp;2.65\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e62.52\u0026plusmn; 2.65\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.09\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45.32\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43.34\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e68.51\u0026thinsp;\u0026plusmn;\u0026thinsp;2.48\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProtein (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.18\u0026thinsp;\u0026plusmn;\u0026thinsp;2.64 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.23\u0026thinsp;\u0026plusmn;\u0026thinsp;5.44\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.03\u0026thinsp;\u0026plusmn;\u0026thinsp;2.41 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.58\u0026thinsp;\u0026plusmn;\u0026thinsp;6.31\u003csup\u003ec3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.06\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.65\u0026thinsp;\u0026plusmn;\u0026thinsp;5.32\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.86\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.71\u0026thinsp;\u0026plusmn;\u0026thinsp;2.64 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.25\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.53\u0026thinsp;\u0026plusmn;\u0026thinsp;5.76\u003csup\u003eb3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNB: Values with different lower - case alphabets superscripts between different drug concentrations along a column were significantly different; while values with different numeric superscripts across a row were significantly different (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Effects of Levetiracetam on oxidative stress and lipid peroxidation indicators of juvenile \u003cem\u003eC. gariepinus\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eThe activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) oxidative stress indicators, on the liver of exposed juvenile \u003cem\u003eC. gariepinus\u003c/em\u003e, were significantly (p\u0026thinsp;\u0026le;\u0026thinsp;0.05) inhibited by levetiracetam from day 5 of exposure, compared to the control (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). At the end of the 10 days exposure period, values reduced from 6.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29 to 2.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26, 0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 to 0.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06 and 8.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.48 to 5.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49 IU/L for control and 0.8mg/L concentration exposed fish, for SOD, CAT, and GPx enzymes respectively. After the 5 days of recovery period, SOD, CAT, and GPx enzymes activity levels of exposed fish, returned to pre-exposure levels, and there was no significant difference (p\u0026thinsp;\u0026ge;\u0026thinsp;0.05) in their activities, when compared to the control (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).The increase in MDA activity, an indication of lipid peroxidation was significantly (p\u0026thinsp;\u0026le;\u0026thinsp;0.05) dose- and duration- dependent, when compared to the control. MDA values increased from 3.5 to 9.5 mg/dL for control and 0.8 mg/dL exposed fish respectively. At the end of the 5 days recovery period, MDA production remained significantly (p\u0026thinsp;\u0026le;\u0026thinsp;0.05) high in all three drug concentrations (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSuperoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx) and activity in juvenile \u003cem\u003eC. gariepinus\u003c/em\u003e on 10-day exposure to and 5-day withdrawal from levetiracetam\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eConc. (mg/l)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eDuration (day)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5-d withdrawal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOD (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.48\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.88\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAT (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003csup\u003ea3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGPx (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.48\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.48\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003csup\u003eb1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.80\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003csup\u003ea2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNB: Values with different lower - case alphabets superscripts between different drug concentrations along a column were significantly different; while values with different numeric superscripts across a row were significantly different (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Effect of Levetiracetam on the Brain Tissue Acetylcholine (AChE) of juvenile \u003cem\u003eC. gariepinus\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eAcetylcholinesterase activity significantly (p\u0026thinsp;\u0026le;\u0026thinsp;0.05) increased from exposure of fish to levetiracetam compared to the control, and values remained significantly (p\u0026thinsp;\u0026le;\u0026thinsp;0.05) higher than those of the control after the 5 days post-exposure period (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.6 Changes in morphological parameters\u003c/h2\u003e \u003cp\u003eChanges in CF and HIS in the fish exposed to levetiracetam are shown in Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e. Though there were concentration- and duration-dependent variations in the CF, they were not significantly different (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). A significant ( p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) increase in HIS occurred on the 10th day in fish exposed to higher concentrations compared to the control, with the highest for 0.8 mg/L of levetiracetam (1.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08 to 1.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18 for control and 0.8 mg/L respectively).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eChanges in correction Factor (CF) and Hepatosomatic indices (HIS) of juvenile \u003cem\u003eC. gariepinus\u003c/em\u003e on 10-day exposure to levetiracetam\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eConc. (mg/L LEV.)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eDuration (day)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5-d withdrawal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.69\u0026plusmn; 0.04 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.57 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHIS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 \u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18 \u003csup\u003eb2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03 \u003csup\u003ea1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNB: Values with different lower-case alphabets superscripts between different drug concentrations along a column were significantly different; while values with different numeric superscripts across a row were significantly different (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003c/div\u003e"},{"header":"4. 0 Discussions","content":"\u003cp\u003eIn this study, \u003cem\u003eC. gariepinus\u003c/em\u003e exposed to levetiracetam manifested various behavioural and stress-related symptoms, such as restlessness (including gasping for air), increased mucus secretion, jerky swimming movement, and loss of equilibrium, at higher concentrations. Similar behavioural and stress-related symptoms were observed in fish exposed to antiepileptic and psychosis drugs such as in \u003cem\u003eC. gariepinus\u003c/em\u003e exposed to chlorpromazine (Atama et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Okpe et al. \u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), \u003cem\u003eCarassius auratus\u003c/em\u003e exposed to chlorpromazine (Li et al. \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e2008\u003c/span\u003e)d \u003cem\u003egariepinus\u003c/em\u003e exposed to diazepam (Ogueji et al. \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e2017b\u003c/span\u003e). Other non-antiepileptic pharmaceuticals that elicited similar behavioural changes in fish were chloramphenicol on \u003cem\u003eC. gariepinus\u003c/em\u003e (Nwani et al. \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e2013a\u003c/span\u003e) and tramadol on \u003cem\u003eDanio rerio\u003c/em\u003e (zebrafish) (Bachour et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Organophosphorus chemicals also elicited similar behavioural responses in \u003cem\u003eC. gariepinus\u003c/em\u003e (Edeh et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), \u003cem\u003eTilapia zilli\u003c/em\u003e (Nwani et al. \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e2013b\u003c/span\u003e) and zebrafish (Koenig et al. \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). The similarities in the behavioural responses of \u003cem\u003eC. gariepinus\u003c/em\u003e and other fish to pharmaceuticals and organophosphorus pesticides, suggest common mechanisms of toxicity and cellular responses. Studies have shown that the highest concentration of antipsychotic drugs is found in the brain for exposed fish, followed by the plasma, and liver and the lowest in the muscle (Huerta et al., \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2016\u003c/span\u003e), indicating that the activities of the drugs are optimal in the fish brain. The behavioural changes observed may be brain function related, especially neurotransmission in fish. Levetiracetam may have a neurotoxic effect on the fish, thus affecting the normal function of the nerves (Miron et al. \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e2005\u003c/span\u003e; Hamed et al. \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn addition to neurotoxicity, Gamma-aminobutyric acid (GABA) receptors have also been implicated in the behavioural changes in antiepileptic drug-treated fish. GABA is a nonprotein amino acid inhibitory neurotransmitter,that occurs naturally in microorganisms, plants, and animals (Sarasa et al. \u003cspan citationid=\"CR81\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). It reduces neuronal excitability by inhibiting nerve transmission receptors in fish brains and so has a calming effect (Allen et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Some antiepileptic drugs are known to bind GABA, reducing its calming effect and inducing high excitability in the fish, which may manifest in behavioural changes such as erratic movement, jerky swimming, and loss of equilibrium (Gupta et al. \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). GABA inhibits the activity of signal-receiving neurons by interacting with the GABA\u003csub\u003eA\u003c/sub\u003e receptors on these cells. GABA-inhibiting drugs include bicuculline, securinine, metrazol and benzodiazepine. Though levetiracetam does not affect GABA directly, studies have shown that levetiracetam promotes inhibition by reducing the negative allosteric effects of Beta carbolines on GABA\u003csub\u003eA\u003c/sub\u003e receptors (Rigo et al. \u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e2002\u003c/span\u003e). Beta-carbolin is naturally occurring and influences brain function, but also exhibits antioxidant effects. It is safe to infer that the causes of behavioural alterations in \u003cem\u003eC. gariepinus\u003c/em\u003e from exposure to levetiracetam are mainly neurotoxicity and GABA \u003csub\u003eA\u003c/sub\u003e receptor inhibition. Exposure of zebrafish to diazepine a GABA\u003csub\u003eA\u003c/sub\u003e receptors-enhancing drug (Campo-Soria et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2006\u003c/span\u003e), has an anxiolytic effect on the fish, thus confirming that fish are sensitive to GABA modulation and supports the hypothesis that exposure to antipsychotic drugs may lead to a mode of action \u0026ndash; mediated effect in fish as it does in humans (Huerta et al. \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). This postulate of mode of action\u0026ndash;mediated effect on fish by antiepileptic drugs may also apply to levetiracetam.\u003c/p\u003e \u003cp\u003eLevetiracetam has anxiogenic properties and thus exerts anxiolytic effects on humans (Werry and Aman \u003cspan citationid=\"CR91\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). In this study, the fish in the treated aquaria at 0.6 and 0.8 mg/L on the 10th day, suppressed preference for the edge of the experimental tank, while the fish in the control showed a preference for the edge of the tanks. This behaviour observed in \u003cem\u003eC. gariepinus\u003c/em\u003e may be an anxiolytic reaction, elicited by the anxiogenic properties of levetiracetam. A similar anxiolytic effect was observed in zebrafish \u003cb\u003e(\u003c/b\u003eBencan et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2009\u003c/span\u003e) and it was attributed to long treatment and high drug concentration regimen. The alteration in behaviour can either enhance or limit the chances of survival of a fish in the wild. For instance, the decreased activity observed in this study, could affect the ability of the fish to forage, migrate, and avoid natural enemies, as well as their reproductive potential. Increased swimming activity though may aid the fish in escaping from predators and finding refuge in more favourable environments, also predisposes the fish of being preyed upon. However, the extra energy spent on swimming will reduce the condition of the fish and may impair their capacity to face additional stressors.\u003c/p\u003e \u003cp\u003eThe mucus secretion noted in the skin and gills of fish has a protective function, but the mucus in the gills may also predispose the fish to respiratory impairments as reported by Birlanga et al. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). They further stated that mucus cells contain mucins and polyanions made up of glycoproteins that trap toxicants and bar the entry of toxicants into the gill epithelium. However, the problem associated with the increased mucus cells is an extension in the distance for gas exchange along the secondary lamellae, consequently reducing the efficiency of gas exchange and thereby inducing hypoxic conditions.\u003c/p\u003e \u003cp\u003eBlood is an essential medium in assessing the health status of animals. Haematological parameters act as physiological indicators of a changing environment due to their relationship with energy, respiration, and defence mechanisms. In this study, the haematological responses of RBC, Hb, and PCV during exposures to leviteracetam decreased resulting in anemia. Similar results have been reported in \u003cem\u003eC. gariepinus\u003c/em\u003e exposed to drugs such as praziquantel (Nwani et al. \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e2016\u003c/span\u003e), ivermectin (Ogueji et al. \u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e2019\u003c/span\u003e) and clotrimazole (Melefa et al. \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). The anaemic effect could be due to levetiracetam toxicity. Hematocrit determined the blood's ratio of plasma to corpuscles and oxygen-carrying capacity. The significant decrease observed in the packed cell volume (PCV) could be attributed to gill damage impaired osmoregulation, and hemodilution due to toxicity. Anaemia impacts on fish growth (Mendez-Martinez et al. 2022). The WBC decreased in all treated fish and during the 5-day withdrawal period compared to the control. Contrary to our findings, increases in WBC were obtained in \u003cem\u003eC. gariepinus\u003c/em\u003e exposed to chloramphenicol (Nwani et al. \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e2013a\u003c/span\u003e), diazepam (Ogueji et al. \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e2017a\u003c/span\u003e), clotrimazole (Melefa et al. \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Ajima et al. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2017\u003c/span\u003e) also reported the elevation of WBC in verapamil-exposed \u003cem\u003eOreochromis niloticus.\u003c/em\u003e This low levels of WBC encountered in this study indicates deteriorative effects on the fish immune system with the consequent release of lymphocytes from lymphomyeloid tissues. Low levels of WBC can be caused by medication, chronic stress and infection (Munker \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e2007\u003c/span\u003e). The leucocyte differentials in \u003cem\u003eC. gariepinus\u003c/em\u003e exposed to levetiracetam were comparable to the control throughout the duration of the experiment, except for the lymphocytes, which were significantly lower than those of the control. This is contrary to the observations recorded in other fishes exposed to different toxicants (Mohammad et al. 2012; Nwani et al. \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Low lymphocyte levels in humans is caused by infections, medication, nutritional deficiency, liver damage, and inflammatory disorder among others (Witeska et al. 2023). In this study, the lymphocytes were the most abundant of the leucocyte differentials. Leucocyte levels decreased from 75% in the control fish to 67% in the exposed fish. The decrease in lymphocytes were responsible for the low level of WBC registered in this study.\u003c/p\u003e \u003cp\u003eThere were no significant differences in the values of MCV, MCH and MCHC in exposed fish compared to the control. Similar to our finding, Nwani et al. (\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e2013b\u003c/span\u003e) reported no significant difference in MCV, MCH and MCHC values in \u003cem\u003eC. gariepinus\u003c/em\u003e exposed to praziquantel. No significant change of MCHC in \u003cem\u003eOnchorrynchus mykiss\u003c/em\u003e exposed to carbamazepine was also reported (Li et al. \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). Contrary to our report however, increased MCV, MCH and MCHC values were reported in \u003cem\u003eC. gariepinus\u003c/em\u003e exposed to clotrimazole (Melefa et al. \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) and acetylsalicylic acid (Siddeswaran et al. \u003cspan citationid=\"CR83\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). The toxicity tests showed haematological changes, indicating toxicity in the treated fish. The haematological profile of \u003cem\u003eC. gariepinus\u003c/em\u003e can be used as a biomarker of distress in response to exposure to the antiepileptic drug levetiracetam.\u003c/p\u003e \u003cp\u003eLevetiracetam-related concentration and duration-dependent elevation in activities of AST, ALT and ALP occurred in \u003cem\u003eC. gariepinus\u003c/em\u003e. The significant increase in these parameters in the exposed fish may be attributed to the hepatotoxic effects of levetiracetam resulting in inflammation and liver damage (Attilakos et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Similar results were obtained by other studies, that recorded an increase in AST and ALT in fish exposed to pharmaceuticals (Nwani et al. \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e2013a\u003c/span\u003e; Ogueji et al. \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e2017a\u003c/span\u003e; Melefa et al. \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Odo et al. \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2020\u003c/span\u003e), increased ALP correlates with the findings of Folarin et al. (2019). For all the biochemical indices observed, the 5-day post-exposure recovery period was not enough to revert the damage. This is an indication that the hepatotoxic effect on the fish was far-reaching and other interventions other than repairs induced by the system, may be needed to repair the damage to the fish's liver.\u003c/p\u003e \u003cp\u003eOxidative stress is a phenomenon caused by an imbalance between the production and accumulation of oxygen-reactive species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products using antioxidants (Pizzino et al. \u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). Antioxidant enzymes play major roles in preventing cellular damage in animals. Superoxide dismutase SOD, a major enzyme in the antioxidant defense systems acts on the Superoxide anion to avoid accumulation of the highly reactive and deleterious O-\u0026sup2; (Biller and Takahashi \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Catalase (CAT) belongs to the group known as the first line of defense antioxidants because it prevents or suppresses free radical formations in the cells (Ighodaro and Akinloye \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). The CAT catalyzes the decomposition of H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e into H\u003csub\u003e2\u003c/sub\u003eO and O\u003csub\u003e2\u003c/sub\u003e, maintaining the balance between ROS formation and elimination (Biller and Takahashi \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2018\u003c/span\u003e).CAT has the function of breaking down hydrogen peroxide, which when in high concentration in the body may lead to complications. Deficiency of catalase is called acatalasemia. GPx neutralizes hydrogen peroxide H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e in the presence of glutathione in water to limit its harmful effects (Biller and Takahashi \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). The study also showed a significant decrease in the activities of the antioxidant enzymes Superoxide dismutase (SOD), Catalase (CAT), and Glutathione peroxidase (GPx), while malondialdehyde (MDA) increased significantly, in the liver among the sexposed groups compared to the control. This is similar to the reports of various authors (Vadhva and Hasan \u003cspan citationid=\"CR88\" class=\"CitationRef\"\u003e1986\u003c/span\u003e; Yadav et al. \u003cspan citationid=\"CR96\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Nwani et al. \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Ogueji et al. \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e2017b\u003c/span\u003e). The inhibition of SOD, CAT and GPx activities in the liver tissues predisposed the fish to inflammation and stress due to increased free radicals (Nwani et al. \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e2016\u003c/span\u003e), resulting in elevated MDA values in the exposed fish. Assessment of LPO is by the measurement of malondialdehyde (Tsikas \u003cspan citationid=\"CR87\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). MDA is one of the final products of polyunsaturated fatty acids peroxidation in the cells. Elevated MDA indicates an increase in lipid peroxidation which leads to a further increase in the production of reactive oxygen species (ROS). The interaction of ROS with biological molecules may cause DNA damage and protein oxidation, resulting in the disturbance of the physiological process (Ogueji et al. \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e2017b\u003c/span\u003e). The elimination of hydroperoxides is part of the cellular defense mechanism against oxidative stress and consequently, lipid peroxidation (Van der Oost et al. \u003cspan citationid=\"CR89\" class=\"CitationRef\"\u003e2003\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eElevated MDA is an indicator of enhanced oxidative stress (Buyukokuroglu et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2002\u003c/span\u003e). Lipid peroxidation (LPO) is an indication of oxidative stress which is formed by the attack of unsaturated fatty acids by free radicals (generated during drug metabolism) in biomembranes (Ayala et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). Continuous increase in Lipid peroxidation can lead to modification of cellular function, and cell and organ damage (Ayala et al. \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2014\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIt is safe to say that, a decrease in SOD, CAT and GPx, was attributed to direct damage of its protein structure by levetiracetam and increasing amounts of hydrogen peroxide produced. This is an indication that levetiracetam in an aquatic environment, could induce oxidative stress in fish. The reduction of CAT, SOD and GPx further encourages the vulnerability of the lymphoid tissues to oxygen metabolites and acid-mediated cell damage. The continuous oxidative damage caused to the cells could disable them and eventually break down completely the self-defense mechanisms of the cells (Biller and Takahashi \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2018\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAcetylcholinesterase (AChE) plays a crucial role in terminating the action of acetylcholine (ACh), a neurotransmitter involved in neuronal communication. By rapidly hydrolyzing acetylcholine, AChE helps restore the synaptic environment to baseline levels, allowing for proper neuronal signaling (Picciotto et al. \u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). Acetylcholinesterase (AChE) activity increased from exposure of fish to levetiracetam. The increase in AChE was significant on day 5 and day 10 of exposure in all three levetiracetam concentrations and day 5 post-exposure period. Similarly, the antipsychotic drug chlorpromazine elevated AChE activities in \u003cem\u003eC. gariepinus\u003c/em\u003e (Atama et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). High acetylcholinesterase level is a compensatory mechanism to decrease the high acetylcholine levels. It results in excessive accumulation of acetylcholine at the neuromuscular junctions and synapses causing symptoms of both muscarinic and nicotinic toxicity. These include increased muscular fasciculation and glandular secretions (Tsai and Tsai \u003cspan citationid=\"CR86\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Acetylcholine is synthesized in the cytosol of nerve terminals and is then stored in synaptic vesicles before exocytotic release. Cholinergic nerve terminals synthesize and release the neurotransmitter acetylcholine. Excessive acetylcholine is known as a cholinergic crisis. High levels of acetylcholine have been reported to be responsible for the restlessness, jerky movement and loss of equilibrium of \u003cem\u003eC. gariepinus.\u003c/em\u003e ACh is also involved in the immune system because it is secreted by the T lymphocytes. Low carbamazepine (CBZ), a classical antiepileptic drug elicited increased AchE activities in the zebrafish (\u003cem\u003eDanio rerio\u003c/em\u003e) brain (Da Silve Santos et al. 2010).\u003c/p\u003e \u003cp\u003eLow protein content was reported in the treated fish. This is similar to reports by Melefa et al. (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) and Okpe et al. (\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Low levels of protein encountered in this study, may be a result of protein oxidation initiated by oxidative stress, produced by the inhibition of antioxidants and elevation of MDA in the treated fish. Protein and glucose are reduced in \u003cem\u003eC. gariepinus\u003c/em\u003e treated with chlorpromazine (Okpe et al. \u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Low glucose levels encountered may be a result of increased swimming which demands more energy and subsequent conversion of more glucose to energy.\u003c/p\u003e \u003cp\u003eWell-being in fish in an environment can be determined by the condition factor and hepatosomatic indices (HIS). In this study, there was no noticeable response of the condition factor to the exposure of levetiracetam. Similar to our findings, Okpe et al. (\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e2023\u003c/span\u003e) reported that the condition factor in \u003cem\u003eC. gariepinus\u003c/em\u003e was not altered when exposed to chlorpromazine. The same was reported when \u003cem\u003eOncorhynchus mykiss\u003c/em\u003e was exposed to carbamazepine (Odo et al. \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Levetiracetam has no significant effect on the ratio of length to weight of the fish. Similar changes were reported in the hepatosomatic index of fish from the influence of pharmaceuticals (Odo et al. \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) and other xenobiotics (Segner et al. \u003cspan citationid=\"CR82\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). HIS values were elevated in \u003cem\u003eC. gariepinus\u003c/em\u003e exposed to levetiracetam. This elevation was significant at 0.6 and 0.8 mg/L on the 10th day of the exposure.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Conclusion\u003c/h2\u003e \u003cp\u003eThe study showed that levetiracetam is toxic to \u003cem\u003eC. gariepinus\u003c/em\u003e. It caused significant alterations in fish behaviour, haematological, serum biochemical and liver antioxidant enzyme profiles at various sub-lethal levels. It decreased the values of Hb, PCV, RBC, and WBC, while MCH, MCV, MCHC, and white blood differentials were the same as the control. Serum biochemical profile AST, ALP, and ALT were elevated indicating that levetiracetam induced damage to liver tissues. Glucose and protein decreased significantly. The activities of antioxidant enzymes such as SOD, CAT, and GPx decreased in liver tissues of \u003cem\u003eC. gariepinus\u003c/em\u003e exposed to sub-lethal levels of levetiracetam, increasing oxidative stress as indicated in the elevated levels of MDA activity. Elevated activities of AChE in sub-lethal concentrations of levetiracetam are indicative of its effect on brain neurotransmission and its anxiolytic impact on \u003cem\u003eC. gariepinus\u003c/em\u003e at high concentrations. The combined use of biochemical and oxidative stress biomarkers using fish models may be useful in the assessment of pharmaceuticals in aquatic ecosystems. Suppression of the urge to take refuge is an anxiolytic and drug mode of action behaviour of \u003cem\u003eC. gariepinus\u003c/em\u003e exposed to high concentrations of levetiracetam. Further studies on the toxicokinetic and toxicodynamics of levetiracetam are necessary for greater insight into the mechanisms of action that induced oxidative stress.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the animal procedures were performed per the standards outlined in the guidelines for the care and use of experimental animals by the Research Ethical Committee of the University of Nigeria, Nsukka. The proposal of this study was approved by the Research Ethical Committee of the University of Nigeria, before the commencement of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe conception of the project topic and design was done by Ekenma Julia Agwu, fish procurement and management by Uba Perpetua Ebube and drug procurement and test concentrations by Inwelegbu Valentine Chukwuemeka. Analysis and results were handled by Joy Ihuoma Nzei. First draft of the manuscript was written by Ekenma Julia Agwu, while all the authors edited and approved the manuscript for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis article did not receive any form of funding.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflict of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData of this study will be made readily available on request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAnderson DP (2003) Text Book of Fish Immunology. 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Sci Total Environ 900:165732\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"environmental-science-and-pollution-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"espr","sideBox":"Learn more about [Environmental Science and Pollution Research](https://www.springer.com/journal/11356)","snPcode":"11356","submissionUrl":"https://submission.nature.com/new-submission/11356/3","title":"Environmental Science and Pollution Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Fish, levetiracetam, morphometric and biochemical changes, haematology, antioxidants","lastPublishedDoi":"10.21203/rs.3.rs-4523849/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4523849/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study investigated the impact of levetiracetam on the multi-biological parameters in juvenile \u003cem\u003eClarias gariepinus\u003c/em\u003e. Fish were exposed to 0.2, 0.6, and 0.8mg/L of levetiracetam and filtered dechlorinated water (control) for 10 days, followed by a recovery period of 5 days. Blood samples were collected periodically for haematological and serum biochemical profiling, and the fish were sacrificed for the liver and brain tissues' analysis. Skin colouration, mucus secretion, and air-gulping increased with concentration and duration of exposure, while swimming rate and opercular movement decreased. A significant (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) dose- and duration-dependent decrease was recorded in the red blood cells, packed cell volume, haemoglobin, and white blood cell counts, while the opposite was recorded in the mean corpuscular haemoglobin, volume, and haemoglobin concentrations. Compared to the control, there were no significant differences in the values of the differential leukocyte counts, except for lymphocytes, which were significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) lower in the highest concentration at the end of the exposure period. Aspartate and alanine aminotransferase, and alkaline phosphatase activities increased significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), while the values for protein and glucose were reduced compared to the control. The oxidative stress biomarkers, liver catalase, superoxide dismutase, and glutathione peroxidase activities decreased significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), while malondialdehyde and acetylcholinesterase activities increased significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) compared to the control. The activities were duration- and concentration-dependent. No significant difference in the correction factor, while the hepatosomatic index decreased significantly (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) compared to the control. The parameters returned to normal after post 5-day withdrawal of levetiracetam administration. The study indicated that levetiracetam is toxic to fish.\u003c/p\u003e","manuscriptTitle":"Effects of Levetiracetam an Antiepileptic Drug on the Multi-biological Parameters in African catfish Clarias gariepinus (Burchell, 1822)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-08 19:52:20","doi":"10.21203/rs.3.rs-4523849/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-01-13T21:07:05+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-01-07T14:25:01+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Environmental Science and Pollution Research","date":"2025-01-07T04:21:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"Environmental Science and Pollution Research","date":"2025-01-03T18:10:09+00:00","index":"","fulltext":""},{"type":"decision","content":"Minor Revision","date":"2024-12-03T12:06:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"environmental-science-and-pollution-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"espr","sideBox":"Learn more about [Environmental Science and Pollution Research](https://www.springer.com/journal/11356)","snPcode":"11356","submissionUrl":"https://submission.nature.com/new-submission/11356/3","title":"Environmental Science and Pollution Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"9d6408e1-7b3b-480f-b2b7-1c7883110dbe","owner":[],"postedDate":"January 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-03-31T15:58:53+00:00","versionOfRecord":{"articleIdentity":"rs-4523849","link":"https://doi.org/10.1007/s11356-025-36281-y","journal":{"identity":"environmental-science-and-pollution-research","isVorOnly":false,"title":"Environmental Science and Pollution Research"},"publishedOn":"2025-03-25 15:56:50","publishedOnDateReadable":"March 25th, 2025"},"versionCreatedAt":"2025-01-08 19:52:20","video":"","vorDoi":"10.1007/s11356-025-36281-y","vorDoiUrl":"https://doi.org/10.1007/s11356-025-36281-y","workflowStages":[]},"version":"v1","identity":"rs-4523849","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4523849","identity":"rs-4523849","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}