Aqueous extract from Cinnamomum zeylanicum (Lauraceae) stem-bark ameliorates gentamicin-induced nephrotoxicity in rats by modulating oxidative stress and inflammatory markers

Aqueous extract from Cinnamomum zeylanicum (Lauraceae) stem-bark ameliorates gentamicin-induced nephrotoxicity in rats by modulating oxidative stress and inflammatory markers | 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 Aqueous extract from Cinnamomum zeylanicum (Lauraceae) stem-bark ameliorates gentamicin-induced nephrotoxicity in rats by modulating oxidative stress and inflammatory markers ATSAMO Albert, LONTSIE Auscar SONGMENE, Mireille Flaure METCHI DONFACK, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-216572/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Nephropathies and especially nephrotoxicity has become one of serious cause of life threatening condition, because of intensive exposure to xenobiotic either by environmental pollution or drug abuse. The present study was undertaken to assess the protective effects of Cinnamomum zeylanicum stem-bark aqueous extract (AECZ) on gentamicin-induced nephrotoxicity. AECZ was prepared by maceration in water and tested orally at the doses of 200 and 400 mg/kg/day to prevent gentamicin induced nephropathies in male Wistar rats. Gentamicin (100 mg/kg/day) was administered for 14 consecutive days by intraperitoneal route, concomitantly with AECZ or silymarin (50 mg/kg/day) used as reference drug. Animal body weight was monitored during the treatment. After the last treatment of the 14 th day, a 24h urine was collected and animals were sacrificed. Blood was collected for the evaluation of hematological and renal function biomarkers. The homogenate of one kidney was used to assess oxidative stress markers and pro-inflammatory cytokine, while the other one was fixed in formaldehyde for histopathological studies. Gentamicin decreased body weight, serum total proteins and calcemia, but increased kidneys relative weight, serum creatinine, urea and uric acid. Moreover, the levels of reduced glutathione, catalase and superoxide dismutase activities were decreased, while an increase in malondialdehyde, proinflammatory cytokines (TNFα, IL-1β, IL-6) and nitrites were observed in negative control group as compared to normal control. Histological analysis of the kidney revealed the presence of tubular necrosis, glomerular degeneration and macrophage infiltration in gentamicin treated group. All these impairment parameters were prevented by AECZ and silymarin treatments. AECZ has a protective effect against gentamicin-induced nephrotoxicity. The antioxidant and anti-inflammatory potentials of this extract may highly contribute to its nephroprotective activity. Urology & Nephrology Toxicology gentamicin nephrotoxicity Cinnamomum zeylanicum antioxidant inflammatory markers Figures Figure 1 Figure 2 Figure 3 Introduction Drug-induced nephrotoxicity is one of the common problem in clinical medicine. Nephrotoxic medications can induced damage to the kidney via various mechanisms, including structural and functional alterations. When evaluating the primary etiologies in renal injury, the incidence of drug-induced toxicity has accounted for 20% of all-cause incidents (Schetz et al, 2005). Numerous drugs go under the category of nephrotoxic medications including gentamicin. Gentamicin (GM), is an aminoglycoside antibiotic agent widely used in clinical practice for the treatment of gram-negative infection (Ullah et al. 2014). However, 10 to 30 % of patients subjected to this drug have a great risk of developing a nephrotoxicity pathology, especially after long-term treatment (Safa et al. 2010; Khan et al. 2011). Mechanisms of GM-induced nephrotoxicity comprises free radicals generation, increase lipids peroxidation, decrease activity of endogenous antioxidant, renal inflammation characterized by macrophage infiltration and subsequent release of proinflammatory cytokines associated with the activation of the stress-induced NF-𝜅B (Kalayarasan et al. 2009; Balakumar et al. 2010; Lee et al. 2012). Several approaches have been tried to reduce gentamicin-nephrotoxicity by utilizing various natural antioxidants, such as Moringa oleifera seeds, Rosmarinus officinalis and Thymus vulgaris (Abdel-Azeem et al. 2017; Nafiu et al. 2019), due to their effectiveness, minimal side effects in clinical use, and relatively low costs. Herbs have many phytochemicals, many of which possess antioxidant activity and can be promising agents against gentamicin-toxicity. Cinnamomum zeylanicum (Lauraceae) also known as true Cinnamon which originates from Sri Lanka and south India, is a tree of about 10 meters high which can withstand hard climatic conditions. It is found predominantly in tropical and subtropical regions where the pluviometry and the temperature range from1500 mm to 2500 mm and from 27°C to 30°C respectively (Kostermans 1983). Their leaves and stem-barks are important and popular spices used worldwide not only for cooking but also in traditional and modern medicines (Balijepalli et al. 2017). Many Cameroonian communities use the stem bark of this plant traditionally for the management of various ailments such as muscular pain, rheumatism, gastrointestinal disorders and typhoid fever (Dongmo et al. 2007). It is also used as an aphrodisiac and an antihypertensive medicine (Nyadjeu et al. 2011). Some Pharmacological investigations carried out on C. zeylanicum have demonstrated a number of important potentials including: anti-nociceptive and anti-inflammatory effects (Atta and Alkofahi 1998), antidiabetic (Verspohl et al. 2005), antihypertensive and vasorelaxant activities (Nyadjeu et al. 2011). The methanol extract of Cinnamomum zeylancum stem bark also demonstrated acute and chronic antihypertensive properties in NO-deficient hypertensive rats (Nyadjeu et al. 2013). Several bioactive compounds such as terpenoids gum, trans-cinnamic acid, phenolic compounds, cinnamaldehyde, eugenol, catechins (Anderson et al. 2004; Jain et al. 2015) have been identified as responsible of the beneficial effects produced by Cinnamomum zeylanicum . Cinnamaldehyde, a phenolic compound primarily identified as the main phytochemicals found in cinnamon bark, is responsible for most of the biological effects of Cinnamomum zeylanicum (Anderson et al. 2004). Various studies have suggested that antifungal, anticancer, antimutagenic, anti-inflammatory, neuroprotective, and antioxidant effects of Cinnamomum zeylanicum are mainly due to the presence of cinnamaldehyde and eugenol (Shaughnessy et al. 2001; Stavinoha and Vattem 2015). It is well established that extracts and oils obtained from cinnamon have strong free radical scavenging or antioxidant activity related to the presence of flavonoids, polyphenolic, and phenolic compounds (Jayaprakasha et al. 2006; Dongmo et al. 2007). Although the nephroprotective activity of the ethanolic extract of Cinnamomum zeylanicum stem barks has been demonstrated (Ullah et al. 2013), no information is presently available as concerning that of the aqueous extract, which is the most common form of preparation used by the population. Besides, mechanisms by which C. zeylanicum protects against kidney damages is not known. The present study was undertaken to determine the preventive effect of AECZ extract in gentamicin-induced nephrotoxicity by investigating the impact of treatment on some renal biomakers, oxidative stress parameters, pro-inflammatory cytokines and histopathological features. Materials And Methods Plant material and preparation of the extract Cinnamomum zeylanicum parts were harvested in Njombe (Littoral region of Cameroon) in August 2018 and used for the authentication of the plant in Yaoundé National Herbarium by comparison with the voucher specimen SRFC/22309. The stem-barks were air-dried at room temperature and ground into a fine powder. Eight hundred grams (800 g) of this powder were macerated in into 7 L of distilled water during 48 hours. The mixture was then filtered with Whatman filter paper N°03. The filtrate was lyophilized and 30.78 g of the aqueous extract was obtained from this preparation (yield of 3.85 %). Animal Material Thirty-six male Wistar rats of 8-9 weeks old, weighing between 135 and 145 g at the beginning of the experiment were obtained from the animal house of the Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I, Cameroon. They were maintained under standard laboratory conditions with natural light cycle and had free access to normal laboratory rat chow and tap water. The study was conducted in accordance with the guidelines of the Cameroon National Ethical Committee of the use of laboratory animals for scientific research (Ref. N◦FWA-IRD 0001954). Animals grouping and experimental design The thirty-six rats were randomized assigned to six groups composed of six animals each and treated daily for 14 days, as follows: a vehicle control group which received distilled water (10 mL/kg, p.o. ) and saline solution 0.9% (1 mL/kg, i.p. ); a negative control group which received distilled water (10 mL/kg, p.o .) and gentamicin (100 mg/kg, i.p. ); a positive control group which received silymarin (50 mg/kg, p.o .) and gentamicin (100 mg/kg, i.p. ), the two test groups which received the aqueous extract of Cinnamomum zeylanicum (AECZ) at the doses of 200 mg/kg and 400 mg/kg ( p.o .) and gentamicin (100 mg/kg, i.p.). The last group, the extract control group was treated with AECZ (400 mg/kg/, p.o.) and saline solution 0.9% (1 mL/kg, i.p .). The doses of the extract were chosen from literature based on their efficiency as nephroprotective substances (Ullah et al. 2013). The oral administration of the plant extract or silymarin was performed one hour before the intraperitoneal injection of gentamicin. Body weight was recorded at the beginning and at the end of the experimental period. At the end of the treatment on the day 15, animals were fasted overnight, but had free access to water. They were then anesthetized with urethane (1.5 g/kg, i.p ) and blood from the carotid arteries was collected using capillary tubes under an anticoagulant (ethylene diamine tetra acetate) or not, for hematological and biochemical studies respectively. After blood collection, the rats were sacrificed by decapitation. The two kidneys were collected, blotted-dry and the relative organ weight was calculated. Measurement of hematological parameters Hematological analysis was performed with blood collected under EDTA using a hematimeter (Mindray BC 3000). The parameters considered were: the red blood cell (RBC) count, the leukocyte (WBC) count, the hemoglobin (Hb) concentration, the hematocrit (HCT), the platelet count, the lymphocyte, the monocyte, and the granulocyte counts. Biochemical and histological analysis Serum was separated from the clotted blood sample by centrifugation at 3000 rpm for 15 min at 4°C and the collected sample was stored at -20 °C for analysis. Glucose, albumin, aspartate amino-transferase, urea, creatinine, uric acid and calcium were assayed in serum samples, using corresponding commercial diagnostic kits purchased from Fortress, UK. Total proteins was evaluated using the method of Bradford (1976). Serum Ca 2+ was evaluated using commercial kit according to procedure provide by the manufacturer. Serum Na + , K + and Cl - were determined using an automatic equipment (Biolyte 2000 - Na + , K + , Cl - /Li+ Diocare cooporation, Thaïlande). One of the collected kidney was homogenized at 20% (w/v) in Tris-HCl 50 mM buffer (pH 7.4). The obtained homogenates were centrifuged at 3000 rpm for 15 minutes at 4°C. The supernatant collected was stored at -20°C for further biochemical assays. The total protein was determined by the method of Bradford (Bradford 1976). The superoxide dismutase (SOD) activity was assessed according to Misra and Fridovish (1972). Reduced glutathione (GSH) and catalase were assayed following the method described by Ellman (1959) and Sinha (1972) respectively. Nitrites content was estimated as described by Slack (1987) while malondialdehyde (MDA) was determined by the method described by Wilbur et al . (1949). The levels of the inflammatory cytokines, interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α), in kidney homogenate were measured using a sandwich enzyme-linked immunoassay kits specific to each cytokine (R&D system, USA). The measurements were performed at 450 nm using a microplate-reading spectrophotometer (Thermo Scientific Multiskan FC). The levels of TNF-α, IL-1β and IL-6 were expressed as pg/mg of protein (El Gamal et al. 2014). For histological analysis, the second kidney was fixed in 10 % formalin for 7 days and further paraffin embedded. Sections of 4-5 μm were made and further stained with hematoxylin and eosin (H&E). The section were examined with light microscope (Ziess Axioscope), digital camera and Minisee software were used for images capture. Statistical analysis Data were expressed as mean ± standard error of mean. Statistical analysis was performed using one-way analysis of Variance (ANOVA) followed by the Tukey post hoc test. P < 0.05 was considered statistically significant. All analyses were performed using Graphpad prism software 8.01 version. Results Effect of C. zeylanicum on the body weight and relative kidney weight Gentamicin significantly ( p < 0.001) decreased the rat weight gain by 45.93% and increased the relative kidney weight by 48.34% as compared to normal control group. AECZ at the doses of 200 and 400 mg/kg significantly ( p < 0.001) prevented the decrease of weight gain and the increase of relative kidney weight by 14.13 % and 17.39 % respectively compared to gentamicin group. AECZ administered alone significantly increased the body weight gain as compared to normal control (Table I). Effects of the stem barks aqueous extract of C. zeylanicum on hematological parameters Table 2 shows the effects of AECZ on some hematological parameters. Apart from the number of monocytes, no other hematological parameter varied significantly regardless of the treatment received. Gentamicin significantly decreased by 52.95 % ( p < 0.001) the number of monocytes compared to the normal control. Silymarin (50 mg/kg), AECZ at the doses of 200 and 400 mg/kg significantly increased the number of monocytes by 52.50 % ( p < 0.05), 90 % ( p < 0.001) and 67.50 % ( p < 0.01) respectively, compared to the group treated only with gentamicin. Effects of the aqueous extract of C. zeylanicum stem barks on serum glucose, albumin, total protein and aspartate amino-transferase The effect of AECZ on serum glucose, total proteins, albumin and aspartate amino-transferase (ASAT) is presented in Table 3. Consecutive to gentamicin administration, it was observed a significant decrease of proteinemia (25 %) as compare to normal control. Compared to GM group, AECZ at the doses of 200 mg/kg and 400 mg/kg significantly inhibited the decrease of proteinemia by 17.30 % ( p < 0.05) and 23.07 % ( p < 0.01), respectively. In the GM group, the serum concentration of albumin increased significantly by 15.91 % ( p < 0.001) compared to normal control group, but concomitant treatment with GM and AECZ at the doses of 200 and 400 mg/kg, significantly (p < 0.001) reduced the serum albumin by 12.83 and 13.73 respectively. The serum concentration of Aspartate amino-transferase increased significantly by 57.7 % (p<0.001) in GM group when compared to normal control. The administration of C. zeylanicum extract at the doses of 200 and 400 mg/kg or Silymarin (50 mg/kg) resulted in a significant reduction in ASAT activity, respectively, by 52.71% ( p < 0.01), 64.70 % ( p < 0.001), and 53.38% ( p < 0.01) as compared to gentamicin intoxicated rats. None of the evaluated parameter was affected by AECZ, when administered alone. Effects of the aqueous extract of C. zeylanicum stem barks on some kidney biomarkers and electrolytes The effects of AECZ on kidney’s function were evaluated by determining the rate of creatinine, uric acid, urea and electrolytes (calcium, potassium, sodium and chloride ions) in serum (Table 4). Gentamicin significantly increased serum creatinine by 77.72%, urea by 131.14%, uric acid by 123.03% and decreased calcemia by 56.56% as compared to normal control. In comparison to negative control group, the two doses of AECZ (200 mg/kg and 400 mg/kg) significantly ( p < 0.001) inhibited the increase of serum creatinine by 43.72% and 47.16%, urea by 57.08% and by 47.16% and uric acid by 57.08% and 47.16% respectively. AECZ at the doses of 200 mg/kg and 400 mg/kg also prevented the decrease of calcemia by 122.48% and 116.06% respectively. Likewise, Silymarin also prevented this decrease. The serum level of potassium and sodium were not significantly affected by any of the treatment as compared to normal control. Effect of the aqueous extract of C. zeylanicum stem barks on renal oxidative stress parameters The effects of the aqueous extract of C. zeylanicum stem barks on some kidney markers of oxidative stress are shown in Figure 1. The renal activity of SOD in the negative control decreased significantly ( p < 0.001) by 73.79 % (10.3 ± 1.14), compared with the normal control group (39.3 ± 5.05). However, pretreatment with Silymarin (50 mg/kg), AECZ (200 mg/kg) and AECZ (400 mg/kg), significantly ( p < 0.001) enhanced superoxide dismutase concentration by about 300.97 %, 406.79 % and 377.66 % (41.30 ± 4.45, 52.20 ± 3.78 and 49.20 ± 4.23, respectively) compared with the gentamicin group (10.30 ± 1.14). Treatment with GM induced a significant decrease ( p < 0.001) in the renal activity of CAT (68.60 ± 2.89) as compared to normal control rats (168.00 ± 11.00). Silymarin (50 mg/kg) significantly increased ( p < 0.001) the activity of CAT in the kidneys by 76.38 % as compared to GM group (121.00 ± 12.7 vs 68.60 ± 2.89). AECZ at the doses of 200 mg/kg and 400 mg/kg significantly enhanced CAT concentration in a dose-dependent manner by about 57.43% (108.00 ± 3.33) and 86.58 % (128.00 ± 7.91) compared to gentamicin group (68.60 ± 2.89). An intraperitoneal injection of rats with gentamicin (100 mg/kg) for 14 days decreased the content of GSH significantly by about 70.87 % (43.40 ± 5.43), compared to the normal control group (168.00 ± 11.01). Moreover, pretreatment with silymarin (50 mg/kg) or AECZ 200 mg/kg and 400 mg/kg one hour before gentamicin administration, caused a significant 2.3, 3.2 and 2.94-fold increases in renal glutathione content (100.00 ± 3.33; 139.00 ± 10.60 and 128.01 ± 7.91), respectively, compared with the gentamicin group ( 43.40 ± 5.43). Gentamicin injection (100 mg/kg/day) for 14 days caused significant elevation ( p < 0.01) of renal lipid peroxidation, which manifested as an increase in malondialdehyde concentration by 1.37 fold (4.37 ± 0.13), compared with the normal control group (3.19 ± 0.02). Pretreatment with silymarin (50 mg/kg), AECZ (200 mg/kg) or AECZ (400 mg/kg) for 14 days before gentamicin, significantly reduced malondialdehyde concentration by about 38.58 %, 38.21 % and 37.75 % reaching (2.64 ± 0.21; 2.70 ± 0.33 and 2.72 ± 0.14), respectively in comparison with the gentamicin group (4.37 ± 0.13). Gentamicin treated rats (negative control) showed significant decrease of 27 % ( p < 0.01) in kidney protein content as compared to normal control, whereas there was a significant increase in total protein content when animals were treated with Silymarin (60.27 %, p < 0.001), AECZ 200 mg/kg (53.42 %, p < 0.001) and AECZ 400 mg/kg (35.61 %, p < 0.01) as compared to GM treated rats. The level of nitrite was increased significantly by 112.64 % ( P < 0.001) in gentamicin-treated rats as compared to normal rats. This concentration of nitrite was decreased significantly by 40.81 % ( P < 0.01) in Silymarin group, by 53.78 % ( p < 0.001) in AECZ (200 mg/kg) group and by 47.02 ( p < 0.001) in AECZ (400 mg/kg) group as compared to GM treated rats. Effect of the aqueous extract of C. zeylanicum stem bark on pro-inflammatory cytokines (TNFα, IL-1β, IL-6). As depicted in Figure 2, when compared to normal control group, GM administration induced a significant ( p < 0.001) 2.21-fold elevation of TNF-𝛼 (116.0 ± 6.3 to 257.0 ± 18.9 pg/mg of protein). However, when this animals were concomitantly treated with Silymarin (50 mg/kg) and GM, a 1.43-fold significantly ( p < 0.001) decreased the TNF-𝛼 levels was noted. In groups treated with AECZ at the doses of 200 and 400 mg/kg, a 1.34-fold and a 1.70-fold decrease of the TNF-𝛼 levels were respectively observed. GM administration induced a significant ( p < 0.001) 2.17-fold elevation of IL-6 (from 39.3 ± 1.72 to 85.4 ± 3.45 pg/mg of protein) when compared to normal control rats. As compared to the GM treated rats, Silymarin (50 mg/kg) significantly ( p < 0.001) decreased the IL-6 levels by 1.81-fold. In groups treated AECZ at the doses of 200 and 400 mg/kg, a significant ( p < 0.001) 1.58-fold and 1.86-fold decrease of the IL-6 level was respectively observed. Figure 2 also shows the effects of AECZ and Silymarin on the levels of IL-1β in GM-treated rats induced treated rats. When Compared to normal control rats, gentamicin induced a 2.26-fold significant ( p < 0.001) elevation of IL-1β (from 22.9 ± 1.31 to 51.9 ± 1.6 pg/mg of protein). As compared to GM group, Silymarin (50 mg/kg) significantly ( p < 0.001) decreased the IL-1β levels by 1.37-fold (from 51.9 ± 1.6 to 37.8± 1.85 pg/mg of protein). Treatment with AECZ at the doses of 200 and 400 mg/kg significantly decreased the level of IL-1β respectively by 1.40-fold ( p < 0.01) and 1.66-fold ( p < 0.001). AECZ administered alone at the dose of 400 mg/kg did no significantly affect the cytokines’ content although a slight increase in IL-1β was noted, when compared to the normal control. Effects of C. zeylanicum aqueous extract on renal histology Microscopically, kidney sections from control rats revealed the normal structure of renal parenchyma (Figure 3A). The kidney of rats in negative control group (Figure 3B) presented many structural alterations including leucocytes infiltration (inflammation), tubular necrosis, tubular clarification, cilia loss, glomerular degeneration, mesangial expansion and significant reduction of urinary space. The architecture of the kidney of rats treated with AECZ at the doses of 200 mg/kg and 400 mg/kg as well as Silymarin (Figures 3C, 3D and 3E respectively) showed no histopathological alterations as compared to normal control group. Discussion The purpose of this work was to evaluate the potential nephroprotective activity of the lyophilized aqueous extract of Cinnamomum zeylanicum stem‑bark in gentamicin-induced nephrotoxicity. Gentamicin (GM) is a typical aminoglycoside widely used for treatment of severe gram-negative bacterial infections. Despite its enormous therapeutic benefits as an antibiotic drug, its clinical use is limited mainly because of its nephrotoxicity side effect (Ali et al. 2005). It has been estimated that up to 30% of patients treated with GM above 7 days show some signs of nephrotoxicity (Paterson et al. 1998). Renal oxidative stress, acute tubular necrosis, glomerular damage and inflammation are some of the major events implicated in gentamicin-induced nephrotoxicity (Jose et al. 2017). In the present study, 14 days of gentamicin injection, reduced body weight gain and increased the kidney relative weight. The decrease of body weight gain could be a result of increased proteolysis, reduced proteins synthesis (Horibe et al. 2004; Adil et al. 2016; Randjelović et al. 2017). The proteolysis and reduced proteins synthesis was confirmed in this study through the decrease of the level of total proteins in the serum and kidneys of gentamicin-treated animal. Any toxic substance that triggers a good functioning of the kidney provokes an inflammatory response in the kidney tissue, as well as it hypertrophies (Witthawaskul et al. 2003; Dhodi et al. 2015); this may justify the increase of relative kidney weight observed in animal group that received gentamicin. The aqueous extract as well as Silymarin significantly improved body weight gain, prevented the decrease of the total serum proteins and the increase of kidney relative weight. Although AECZ administered alone significantly increased the body weight gain, it did not affect the protein content, rolling out a probable effect of this extract on the protein synthesis. It is therefore, more likely that it instead prevent the proteolysis. Apart from the monocyte count, which decreased in animals treated with gentamicin, no other hematological parameter varied significantly independently of the treatment. This can be justified by the relatively short duration of treatment which was not enough to be able to induce any modification of the erythropoietin content. The decrease in the number of monocytes in the blood could be explained by their migration from the blood stream to the injured tissues. Electrolyte balance is essential for normal homeostasis. Aminoglycosides cause derangements of renal functions by accumulating on the membranes of the proximal convoluted tubule, disturbing the reabsorption and secretion of electrolytes and in that way causes homeostatic imbalance. In the present study, serum calcium was reduced significantly and a non-significant decrease in serum sodium and potassium in gentamicin treated rats were observed. These observations on serum sodium and potassium levels although non-significant, are in agreement with those of Nafiu et al. (2019) showing that serum sodium and potassium reduction were observed in gentamicin treated rats, indicative of lesions in renal tubular epithelium and despair of Na + –K + ATPase by gentamicin. Studies in animal and human have demonstrated that gentamicin and other aminoglycosides impair calcium transport in the renal tubules and, in some instances, result in a significant increase in urinary calcium excretion and in that way causes hypocalcemia (Randjelović et al. 2017). AECZ as well as Silymarin inhibited the decrease of calcemia in this study. This effect may be due to the antioxidative properties of AECZ which prevented the cell membranous lipids peroxidation and tubular cell necrosis. One of the mechanism through which gentamicin induces nephrotoxicity is by causing a significant increase, in the blood stream, of the levels of renal function markers such as creatinine, urea, uric acid, albumin and ASAT, indicating renal dysfunction (Jain and Singhai 2010; Safa et al. 2010). Administration of AECZ or Silymarin along with gentamicin caused significant decrease in the concentration of creatinine, urea, uric acid, albumin and ASAT while a significant increase in total protein in the serum was noted, suggesting a protective effect of AECZ or Silymarin. Similar protective studies of different extracts against gentamicin have been reported previously (El-Tantawy et al. 2013; El Gamal et al. 2014). Gentamicin generates reactive oxygen species (ROS) in the kidney. ROS are a trigger of oxidative stress, which is the gateway to inflammatory pathways. It has been reported that during inflammation, different type of cells, e.g. macrophages and neutrophils play a major role in the production of reactive oxygen species, that will create antioxidant imbalance and the peroxidation of cell components (El-Tantawy et al. 2013). Therefore, free radicals are a critical determining factor that plays an important role in the mechanism leading to the induction of pro-inflammatory mediators. Oxidative stress is one of the major causes for emerging acute and chronic disorders. Results confirmed that after gentamicin administration, the levels of various tissue antioxidant like SOD, reduced-glutathione and catalase were decreased significantly in rats. This declined results in increasing lipid peroxidation which also play a major role in gentamicin-induced nephrotoxicicty (Jose et al. 2017). It is well established that extracts and oils obtained from Cinnamomum zeylanicum have strong free radical scavenging or antioxidant activity due to the presence of flavonoids, polyphenolic, and phenolic compounds in the cinnamon (Jayaprakasha et al. 2006). In the present study, AECZ or Silymarin administration reduced oxidative stress by inhibition of lipid peroxidation therefore boosted the activity of SOD, CAT and glutathione. Vasodilator effects of NO appear to play a role in GM-induced nephrotoxicity (Christo et al. 2011). In fact, NO seems to increase renal injury through its reaction with superoxide radical (O 2 - ), generating the highly cytotoxic peroxynitrite oxidant (Koppenol et al. 1992). Gentamicin treatment induced an increase in nitric oxide levels which in turn increase inflammation that ultimately leads to cellular damage. In the present study, gentamicin treatment induced an increase in the nitric oxide level, therefore, increasing the inflammation leading to cellular damage. The AECZ or Silymarin treatment significantly attenuate nitric oxide induced oxidative stress leading to reduction in inflammation. To confirm this, the effects of AECZ or silymarin were evaluated on the levels of some pro-inflammatory markers. The role of various pro-inflammatory mediators such as TNFα, IL-6 and IL- 1β, are well known in the kidney diseases (El Gamal et al. 2014; Jose et al. 2017). In this study, AECZ (200 and 400 mg/kg) or silymarin (50 mg/kg) significantly downregulates the renal proinflammatory cytokines (TNF-𝛼, IL-6 and IL- 1β). These findings corroborate those of earlier studies demonstrating that plant extracts are able to reverse the increasing of pro-inflammatory cytokines induced by gentamicin (Joshi et al. 2010; Erjaee et al. 2015; Jose et al. 2017). Previous study on the hydroalcoholic extract of Cinnamomum zeylanicum stem bark on nociception and anxiety showed that this anti-inflammatory effect is ascribed to trans-cinnamaldehyde component of Cinnamon (Chao et al. 2008; Seema and Sparsh 2019). Thus, the anti-inflammatory effect observed in this study may be due to the reduction of inflammatory mediators release. Evidences have indicated that the renal toxicity of gentamicin is due to its selective accumulation in the renal proximal convoluted tubules which subsequently leads to the loss of the tubule brush border integrity, severe degenerationnecrosis in epithelial cells of the proximal tubules, and infiltration of mononuclear cells in intertubular spaces (Lopez-Novoa et al. 2011; Raju et al. 2011). In this study, the microscopic analysis of the kidney tissues revealed the nephrotoxic effect of gentamicin. The histological analyses of kidney sections from gentamicin-treated animals (negative control) showed inflammations, fibrosis, tubular clarifications, glomerular hypertrophy and degeneration with a reduced urinary space. Previous studies described as well these renal tissue damages induced by gentamicin (Dhodi et al. 2015; Randjelović et al. 2017). The histological analysis of kidney sections from animals treated with AECZ (200 mg/kg and 400 mg/kg) as well as Silymarin presented an aspect similar to that of normal animals. This shows that AECZ prevented the renal tissues damages of the gentamicin. This histopathological observations correlate the pathologic variations of the biochemical values. The animals that were treated with AECZ (400 mg/kg) alone showed no pathological changes. This indicates that AECZ does not possess any adverse effects. Phytochemical screening of extract revealed the presence of several active principles such as phenolic compounds, flavonoids, tannins and saponins (Mallavarapu and Rajeswara 2007). Thus, the nephroprotective effect observed in the present study might be due to the presence of these active constituents especially E-cinnamaldehyde and o-methoxy cinnamaldehyde, eugenol and cinnamic acid which are the major compounds isolated from Cinnamomum zeylanicum (Seema and Sparsh 2019). Conclusion According to the results obtained in the present study, AECZ has a potential to prevent kidney damages. AECZ protect against gentamicin induced kidney toxicity by inhibiting oxidative stress, lipid peroxidation, inflammation and thereby suppressed the pro-inflammatory cytokines such as TNF-α, IL 1β, IL-6 and protect kidney tissues for necrosis. AECZ might be a good candidate for the development of new drugs that can protect against acute kidney diseases. Abbreviations AECZ : Cinnamomum zeylanicum stem-bark aqueous extract ANOVA: One Way Analysis of Variance ASAT: Aspartate Amino-Transferase CAT: Catalase DG: glomerular degeneration. DT: distal tubule EDTA: Ethylenediaminetetraacetic acid G: glomeruli GM : Gentamicin GSH: Reduced glutathione H&E: Hematoxylin and Eosin Hb: hemoglobin HCT: hematocrit IL: Interleukin LI: leucocyte infiltrations MDA: malondialdehyde NF-𝜅B: Nuclear Factor-kappa B NO: Nitric Oxide PT: proximal tubule RBC: Red Blood Cell ROS : Reactive Oxygen Species SEM: Standard Error of Mean Sily 50: silymarin (50 mg/kg). SOD: superoxide dismutase TC: tubular clarification TNFα: Tumor Necrosing Factor UK: United Kingdom US: urinary space USA: United Stated of America WBC: White Blood Cell References Abdel-Azeem AS, Hegazy AM, Zeidan HM, et al (2017) Potential Renoprotective Effects of Rosemary and Thyme Against Gentamicin Toxicity in Rats. 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J Ethnopharmacol 89:115–121. https://doi.org/10.1016/S0378-8741(03)00273-3 Tables Table 1 : Effects of C.zeylanicum stem bark aqueous extract on body weight and relative kidney weight NC GM Sily 50 + GM AECZ 200 + GM AECZ 400 + GM AECZ 400 BW D1 (g) 139.16 ± 8.93 143.33 ± 10.01 134.33 ± 8.81 139.00 ± 10.41 140.33 ± 5.91 140.66 ± 7.81 BW D14 (g) 179.88 ± 3.96 161.40 ± 6.78 174.61 ± 7.61 191.13 ± 8.79 178.50 ± 3.23 190.21 ± 4.13 ΔBW D14-D1 (%) 29.24 ± 1.49 15.81 ± 0.48 z 33.03 ± 1.11 c 39.05 ± 2.64 c 33.66 ± 2.07 c 40.51 ± 1.13 z Relative kidney weight (g/100g BW) 0.62 ± 0.01 0.92 ± 0.01 Z 0.72 ± 0.01 c 0.79 ± 0.01 c 0.76 ± 0.02 c 0.67 ± 0.01 Each value represents the mean ± SEM. n = 6; z p < 0.001 significant difference as compare to normal control. c p < 0.001 significant difference as compare to negative control. BW = body weight, ΔBW = variation of body weight, D = day, NC = normal control, GM = gentamicin, AECZ = stem barks aqueous extract of Cinnamomum zeylanicum , Sily 50 = silymarin (50.mg/kg). Tableau 2: Effects of C. zeylanicum stem bark aqueous extract on some hematological parameters Parameters NC GM Sily 50 + GM AECZ 200 + GM AECZ 400 + GM AECZ 400 WBC (x 10 3 /μL) 6.30 ± 0.67 52.6 ± 0.71 6.01 ± 0.94 7.25 ± 0.89 6.15 ± 0.87 6.20 ± 0.49 Lympho (x10 3 /μL) 3.51 ± 0.22 26.8 ± 0.28 3.44 ± 0.51 4.00 ± 0.55 3.97 ± 0.49 3.47 ± 0.38 Mono (x 10 3 /μL) 0.85 ± 0.03 0.40 ± 0.04 z 0.61 ± 0.03 a 0.76 ± 0.06 c 0.67 ± 0.06 b 0.61 ± 0.05 Granulo (x 10 3 /μL) 1.45 ± 0.17 1.44 ± 0.11 1.15 ± 0.20 1.45 ± 0.20 1.24 ± 0.15 1.56 ± 0.08 RBC (x 10 6 /μL) 6.92 ± 0.14 6.77 ± 0.28 7.02 ± 0.10 7.09 ± 0.12 6.82 ± 0.18 6.88 ± 0.24 PLT (x 10 3 /μL) 472.6 ± 7.6 466.6 ± 46.6 458.1 ± 48.2 522.8 ± 48.2 457.5 ± 32.1 29.5 ± 35.7 Hb (g/dL) 13.31 ± 0.18 12.93 ± 0.64 13.25 ± 0.35 13.91 ± 0.20 12.53 ± 0.51 13.01 ± 0.54 HTC (%) 36.41 ± 1.41 34.41 ±2.55 34.86 ± 1.85 36.50 ± 1.53 33.916 ± 1.09 35.65 ± 2.35 Each value represents the mean ± SEM. n = 6; z p < 0.001 significant differences as compare to normal control. ; a p < 0.05, b P < 0.01, c p < 0.001 significant difference compare to gentamicin group. NC = normal control, GM: gentamicin, AECZ: stem barks aqueous extract of Cinnamomum zeylanicum , Sily 50: silymarine (50 mg/kg). WBC: white blood cells, Lympho : lymphocytes, Mono : monocytes, Granulo : granulocytes, RBC : Red blood cells, Hb : hemoglobin, PLT : platelets, HTC =hematocrit. Table 3: Effects of C. zeylanicum stem bark aqueous extract on serum glucose, total proteins, albumin and aspartate amino-tranferase Parameters NC GM Sily 50 + GM AECZ 200 + GM AECZ 400 + GM AECZ 400 TP (mg/dL) 130 ± 0.02 104 ± 0.01 y 120 ± 0.01 a 122 ± 0.01 a 128 ± 0.03 b 129 ± 0.04 Albumin (mg/dL) 57.80 ± 1.05 67.00 ± 1.35 z 57.50 ± 1.28 c 58.40 ± 1.01 c 57.80 ± 0.84 c 56.50 ± 1.49 Glucose (mg/dL) 71.66 ± 7.04 68.04 ± 6.84 71.99 ± 6.37 73.60 ± 7.21 67.58 ± 3.63 65.73 ± 6.09 ASAT (UI) 172.54± 32.43 407.81 ± 79.83 z 190.11 ± 27.84 b 192.85 ± 23.56 b 143.99 ± 20.18 c 148.94 ± 7.08 Each value represents the mean ± SEM. n = 6; y p< 0.01, z p < 0,001 significant difference as compare to normal control. a p < 0.05, b p < 0.01, c p < 0.001 significant differences as compare to negative control. NC = normal control, GM = gentamicin, AECZ = stem barks aqueous extract of Cinnamomum zeylanicum , Sily 50 = silymarin (50 mg/kg), TP: total proteins, ASAT = Aspatate Amino-Transferase Table 4 : Effects of C. zeylanicum stem bark aqueous extract on some renal function biomarkers and electrolytes Parameters NC GM Sily 50 + GM AECZ 200 + GM AECZ 400 + GM AECZ 400 Creatinine (mg/dL) 0.57 ± 0.02 1.02 ± 0.09 z 0.35 ± 0.05 c 0.57 ± 0.04 c 0.55 ± 0.03 c 0.51 ± 0.05 Urea (mg/dL) 21.80 ± 1.73 50.39 ± 3.56 z 20.89 ± 1.54 c 26.49 ± 2.55 c 21.69 ± 2.31 c 25.13 ± 2.36 uric Acid (mg/dL) 2.44 ± 0.12 5.45 ± 0.87 z 2.49 ± 0.12 c 2.34 ± 0.15 c 2.88 ± 0.14 c 2.31 ± 0.14 Ca 2+ (mg/dL) 4.82 ± 0.50 1.94 ± 0.15 y 4.43 ± 0.37 a 4.34 ± 0.67 a 4.21 ± 0.78 a 4.66 ± 0.54 K + (mEq/L) 5.44 ± 0.25 4.70 ± 0.81 5.20± 0.36 5.52 ± 0.27 5.92 ± 0.49 5.50 ± 0.20 Na + (mEq/L) 140.80 ± 1.15 134.00 ± 0.70 142.60 ± 0.67 135.20 ± 5.39 143.40 ± 0.50 141.00 ± 1.44 Cl - (mEq/L) 105.80 ± 1.01 104.20 ± 1.20 104.00 ± 0.66 108.20 ± 0.96 105.20 ± 1.49 105.00 ± 1.14 Each value represents the mean ± SEM. n = 6; y p < 0.01, z p < 0.001 significant differences as compare to normal control. a p < 0.01, c p < 0.001 significant differences as compare to negative control. NC = normal control, GM = gentamicin, AECZ = stem barks aqueous extract of Cinnamomum zeylanicum , Sily 50 = silymarin (50 mg/kg). Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-216572","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":11722747,"identity":"32cf6dcf-022e-444c-88ef-426dee21cd90","order_by":0,"name":"ATSAMO Albert","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYBADGQMQ+YGBIQFK4wFsEIoHqIWxcQZEC+MMorU08xCjhX9++8NPNyrseMzZe58/tm2zy+Nnb2BsrsCjReIYj7F0zplkHsue44bNuW3JxZI9Bxgbz+Cz5hgPg3RuGzOPwY00RqAW5sQNNxLYHzbg0SF/jP3x79y2eh6D+88Ymy3b6kFaGBvxaTE4xmAGtOUw0BY2xmbGtsOEtRgeyzGzzjlzHOiXNMaZPeeOJ87sOdiIV4vc4eOPb+dUVMuZsx9j+PCjrDqxn735IF4tqIARHEuMxGsAgj+kKB4Fo2AUjIKRAgCTyFCQK0yenAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-6788-0351","institution":"University of Yaounde I: Universite de Yaounde I","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"ATSAMO","middleName":"","lastName":"Albert","suffix":""},{"id":11722748,"identity":"cfa01ea8-5610-4690-90ae-1acac8d26498","order_by":1,"name":"LONTSIE Auscar SONGMENE","email":"","orcid":"","institution":"University of Yaounde I: Universite de Yaounde I","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"LONTSIE","middleName":"Auscar","lastName":"SONGMENE","suffix":""},{"id":11722749,"identity":"7bab0f60-be6a-4056-936d-cdb72332731b","order_by":2,"name":"Mireille Flaure METCHI DONFACK","email":"","orcid":"","institution":"University of Yaounde I: Universite de Yaounde I","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mireille","middleName":"Flaure METCHI","lastName":"DONFACK","suffix":""},{"id":11722750,"identity":"6cc01099-a89b-467b-af67-6d5cec6f8d21","order_by":3,"name":"Omer Bébé NGOUATEU KENFACK","email":"","orcid":"","institution":"University of Yaounde I: Universite de Yaounde I","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Omer","middleName":"Bébé NGOUATEU","lastName":"KENFACK","suffix":""},{"id":11722751,"identity":"6290b662-9cca-4473-afb5-6fc13fdcbdcc","order_by":4,"name":"Télesphore Benoît NGUELEFACK","email":"","orcid":"","institution":"University of Dschang: Universite de Dschang","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Télesphore","middleName":"Benoît","lastName":"NGUELEFACK","suffix":""},{"id":11722752,"identity":"ede7f96e-9461-4fbe-b403-3cd8460943ae","order_by":5,"name":"Théophile DIMO","email":"","orcid":"","institution":"University of Yaounde I: Universite de Yaounde I","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Théophile","middleName":"","lastName":"DIMO","suffix":""}],"badges":[],"createdAt":"2021-02-07 04:39:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-216572/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-216572/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":6118529,"identity":"06d62927-1dd6-4677-8da2-c66516e88dfa","added_by":"auto","created_at":"2021-02-19 00:39:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":167637,"visible":true,"origin":"","legend":"Effects of Cinnamomum zeylanicum stem bark aqueous extract on kidney oxidative stress parameters\nEach bar represents the mean ± SEM. n = 6; *p \u003c 0.05, **p \u003c 0.01, ***p \u003c 0.001 significant differences as compared to normal control. ap \u003c 0.05, bp \u003c 0.01, cp \u003c 0.001 significant differences as compared to gentamicin group. NC: normal control, AECZ: stem barks aqueous extract of Cinnamomum zeylanicum, Sily 50 = silymarin (50 mg/kg).\n","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-216572/v1/437c726a4f4f1fe2684d1b1c.png"},{"id":6118528,"identity":"e360b2eb-0c03-49e9-aeea-e1cc093c8257","added_by":"auto","created_at":"2021-02-19 00:39:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":120489,"visible":true,"origin":"","legend":"Effects of Cinnamomum zeylanicum stem bark aqueous extract on proinflammatory cytokines\nEach bar represents the mean ± SEM. n = 6; *p \u003c 0.05, **p \u003c 0.01, ***p \u003c 0.001 significant differences as compared to normal control. bp \u003c 0.01, cp \u003c 0.001 significant differences as compared to gentamicin group. NC: normal control, AECZ: stem barks aqueous extract of Cinnamomum zeylanicum, Sily 50 = silymarin (50 mg/kg).\n","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-216572/v1/3fe6374f00d3bd157da21cb7.png"},{"id":6118319,"identity":"05a1a8c5-fe40-4c05-ad39-9f9f4037c421","added_by":"auto","created_at":"2021-02-19 00:36:22","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2077819,"visible":true,"origin":"","legend":"Microphotographs of the kidney tissue (H\u0026E, × 400): A (normal control), B (negative control), C (positive control), D (Extract at the dose of 200 mg/kg + GM), E (Extract at the dose of 400 mg/kg + GM), F (Extract at the dose of 400 mg/kg only). \nG: glomeruli, US: urinary space, PT: proximal tubule, DT: distal tubule, LI: leucocyte infiltrations, TC: tubular clarification, DG: glomerular degeneration. GM = gentamicin, AECZ = aqueous extract of C. zeylanicum, Sily 50 = silymarin (50 mg/kg).\n","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-216572/v1/cb8d08b533a4c8bf5b8aba70.png"},{"id":15670883,"identity":"f0ea1a49-0c22-4974-93e8-015b6c6cac05","added_by":"auto","created_at":"2021-11-18 14:02:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2811644,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-216572/v1/54a61096-a8a2-4d96-9a9c-6223540f41d4.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eAqueous extract from \u003cem\u003eCinnamomum zeylanicum\u003c/em\u003e (Lauraceae) stem-bark ameliorates gentamicin-induced nephrotoxicity in rats by modulating oxidative stress and inflammatory markers\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDrug-induced nephrotoxicity is one of the common problem in clinical medicine. Nephrotoxic medications can induced damage to the kidney via various mechanisms, including structural and functional alterations. When evaluating the primary etiologies in renal injury, the incidence of drug-induced toxicity has accounted for 20% of all-cause incidents (Schetz et al, 2005). Numerous drugs go under the category of nephrotoxic medications including gentamicin. Gentamicin (GM), is an aminoglycoside antibiotic agent widely used in clinical practice for the treatment of gram-negative infection (Ullah et al. 2014). However, 10 to 30 % of patients subjected to this drug have a great risk of developing a nephrotoxicity pathology, especially after long-term treatment (Safa et al. 2010; Khan et al. 2011). Mechanisms of GM-induced nephrotoxicity comprises free radicals generation, increase lipids peroxidation, decrease activity of endogenous antioxidant, renal inflammation characterized by macrophage infiltration and subsequent release of proinflammatory cytokines associated with the activation of the stress-induced NF-𝜅B (Kalayarasan et al. 2009; Balakumar et al. 2010; Lee et al. 2012). Several approaches have been tried to reduce gentamicin-nephrotoxicity by utilizing various natural antioxidants, such as \u003cem\u003eMoringa oleifera \u003c/em\u003eseeds, \u003cem\u003eRosmarinus officinalis\u003c/em\u003e and \u003cem\u003eThymus vulgaris\u003c/em\u003e (Abdel-Azeem et al. 2017; Nafiu et al. 2019), due to their effectiveness, minimal side effects in clinical use, and relatively low costs. Herbs have many phytochemicals, many of which possess antioxidant activity and can be promising agents against gentamicin-toxicity.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCinnamomum zeylanicum\u003c/em\u003e (Lauraceae) also known as true Cinnamon which originates from Sri Lanka and south India, is a tree of about 10\u0026nbsp;meters high which can withstand hard climatic conditions. It is found predominantly in tropical and subtropical regions where the pluviometry and the temperature range from1500 mm to 2500 mm and from 27\u0026deg;C to 30\u0026deg;C respectively (Kostermans 1983). Their leaves and stem-barks are important and popular spices used worldwide not only for cooking but also in traditional and modern medicines (Balijepalli et al. 2017).\u003c/p\u003e\n\u003cp\u003eMany Cameroonian communities use the stem bark of this plant traditionally for the management of various ailments such as muscular pain, rheumatism, gastrointestinal disorders and typhoid fever (Dongmo et al. 2007). It is also used as an aphrodisiac and an antihypertensive medicine (Nyadjeu et al. 2011). Some Pharmacological investigations carried out on \u003cem\u003eC. zeylanicum\u003c/em\u003e have demonstrated a number of important potentials including: anti-nociceptive and anti-inflammatory effects (Atta and Alkofahi 1998), antidiabetic (Verspohl et al. 2005), antihypertensive and vasorelaxant activities (Nyadjeu et al. 2011). The methanol extract of \u003cem\u003eCinnamomum zeylancum\u003c/em\u003e stem bark also demonstrated acute and chronic antihypertensive properties in NO-deficient hypertensive rats (Nyadjeu et al. 2013).\u003c/p\u003e\n\u003cp\u003eSeveral bioactive compounds such as terpenoids gum, trans-cinnamic acid, phenolic compounds, cinnamaldehyde, eugenol, catechins (Anderson et al. 2004; Jain et al. 2015) have been identified as responsible of the beneficial effects produced by \u003cem\u003eCinnamomum zeylanicum\u003c/em\u003e. Cinnamaldehyde, a phenolic compound primarily identified as the main phytochemicals found in cinnamon bark, is responsible for most of the biological effects of \u003cem\u003eCinnamomum zeylanicum \u003c/em\u003e(Anderson et al. 2004). Various studies have suggested that antifungal, anticancer, antimutagenic, anti-inflammatory, neuroprotective, and antioxidant effects of \u003cem\u003eCinnamomum zeylanicum \u003c/em\u003eare mainly due to the presence of cinnamaldehyde and eugenol (Shaughnessy et al. 2001; Stavinoha and Vattem 2015). It is well established that extracts and oils obtained from cinnamon have strong free radical scavenging or antioxidant activity related to the presence of flavonoids, polyphenolic, and phenolic compounds (Jayaprakasha et al. 2006; Dongmo et al. 2007).\u003c/p\u003e\n\u003cp\u003eAlthough the nephroprotective activity of the ethanolic extract of\u003cem\u003e Cinnamomum zeylanicum\u003c/em\u003e stem barks has been demonstrated (Ullah et al. 2013), no information is presently available as concerning that of the aqueous extract, which is the most common form of preparation used by the population. Besides, mechanisms by which \u003cem\u003eC. zeylanicum\u003c/em\u003e protects against kidney damages is not known. The present study was undertaken to determine the preventive effect of AECZ extract in gentamicin-induced nephrotoxicity by investigating the impact of treatment on some renal biomakers, oxidative stress parameters, pro-inflammatory cytokines and histopathological features.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003e\u003cstrong\u003ePlant material and preparation of the extract \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCinnamomum zeylanicum\u003c/em\u003e parts were harvested in Njombe (Littoral region of Cameroon) in August 2018 and used for the authentication of the plant in Yaound\u0026eacute; National Herbarium by comparison with the voucher specimen SRFC/22309. The stem-barks were air-dried at room temperature and ground into a fine powder. Eight hundred grams (800 g) of this powder were macerated in into 7 L of distilled water during 48 hours. The mixture was then filtered with Whatman filter paper N\u0026deg;03. The filtrate was lyophilized and 30.78 g of the aqueous extract was obtained from this preparation (yield of 3.85 %).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnimal Material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThirty-six male Wistar rats of 8-9 weeks old, weighing between 135 and 145 g at the beginning of the experiment were obtained from the animal house of the Department of Animal Biology and Physiology, Faculty of Science, University of Yaound\u0026eacute; I, Cameroon. They were maintained under standard laboratory conditions with natural light cycle and had free access to normal laboratory rat chow and tap water. The study was conducted in accordance with the guidelines of the Cameroon National Ethical Committee of the use of laboratory animals for scientific research (Ref.\u0026nbsp;N◦FWA-IRD 0001954).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnimals grouping and experimental design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe thirty-six rats were randomized assigned to six groups composed of six animals each and treated daily for 14 days, as follows: a vehicle control group which received distilled water (10 mL/kg, \u003cem\u003ep.o.\u003c/em\u003e) and saline solution 0.9% (1\u0026nbsp;mL/kg, \u003cem\u003ei.p.\u003c/em\u003e); a negative control group which received distilled water (10 mL/kg, \u003cem\u003ep.o\u003c/em\u003e.) and gentamicin (100 mg/kg, \u003cem\u003ei.p.\u003c/em\u003e); a positive control group which received silymarin (50\u0026nbsp;mg/kg, \u003cem\u003ep.o\u003c/em\u003e.) and gentamicin (100 mg/kg, \u003cem\u003ei.p.\u003c/em\u003e), the two test groups which received the aqueous extract of \u003cem\u003eCinnamomum zeylanicum\u003c/em\u003e (AECZ) at the doses of 200 mg/kg and 400 mg/kg (\u003cem\u003ep.o\u003c/em\u003e.) and gentamicin (100 mg/kg, i.p.). The last group, the extract control group was treated with AECZ (400 mg/kg/, p.o.) and saline solution 0.9% (1 mL/kg, \u003cem\u003ei.p\u003c/em\u003e.). The doses of the extract were chosen from literature based on their efficiency as nephroprotective substances (Ullah et al. 2013). The oral administration of the plant extract or silymarin was performed one hour before the intraperitoneal injection of gentamicin. Body weight was recorded at the beginning and at the end of the experimental period.\u003c/p\u003e\n\u003cp\u003eAt the end of the treatment on the day 15, animals were fasted overnight, but had free access to water. They were then anesthetized with urethane (1.5 g/kg, \u003cem\u003ei.p\u003c/em\u003e) and blood from the carotid arteries was collected using capillary tubes under an anticoagulant (ethylene diamine tetra acetate) or not, for hematological and biochemical studies respectively. After blood collection, the rats were sacrificed by decapitation. The two kidneys were collected, blotted-dry and the relative organ weight was calculated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeasurement of hematological parameters\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHematological analysis was performed with blood collected under EDTA using a hematimeter (Mindray BC 3000). The parameters considered were: the red blood cell (RBC) count, the leukocyte (WBC) count, the hemoglobin (Hb) concentration, the hematocrit (HCT), the platelet count, the lymphocyte, the monocyte, and the granulocyte counts.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBiochemical and histological analysis \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSerum was separated from the clotted blood sample by centrifugation at 3000 rpm for 15 min at 4\u0026deg;C and the collected sample was stored at -20 \u0026deg;C for analysis. Glucose, albumin, aspartate amino-transferase, urea, creatinine, uric acid and calcium were assayed in serum samples, using corresponding commercial diagnostic kits purchased from Fortress, UK. Total proteins was evaluated using the method of Bradford (1976). Serum Ca\u003csup\u003e2+\u003c/sup\u003e was evaluated using commercial kit according to procedure provide by the manufacturer. Serum Na\u003csup\u003e+\u003c/sup\u003e, K\u003csup\u003e+\u003c/sup\u003e and Cl\u003csup\u003e-\u003c/sup\u003e were determined using an automatic equipment (Biolyte 2000 - Na\u003csup\u003e+\u003c/sup\u003e, K\u003csup\u003e+\u003c/sup\u003e, Cl\u003csup\u003e-\u003c/sup\u003e/Li+ Diocare cooporation, Tha\u0026iuml;lande).\u003c/p\u003e\n\u003cp\u003eOne of the collected kidney was homogenized at 20% (w/v) in Tris-HCl 50 mM buffer (pH 7.4). The obtained homogenates were centrifuged at 3000 rpm for 15 minutes at 4\u0026deg;C. The supernatant collected was stored at -20\u0026deg;C for further biochemical assays. The total protein was determined by the method of Bradford (Bradford 1976). The superoxide dismutase (SOD) activity was assessed according to Misra and Fridovish (1972). Reduced glutathione (GSH) and catalase were assayed following the method described by Ellman (1959) and Sinha (1972) respectively. Nitrites content was estimated as described by Slack (1987) while malondialdehyde (MDA) was determined by the method described by Wilbur \u003cem\u003eet al\u003c/em\u003e. (1949).\u003c/p\u003e\n\u003cp\u003eThe levels of the inflammatory cytokines, interleukin 1\u0026beta; (IL-1\u0026beta;), IL-6, and tumor necrosis factor \u0026alpha; (TNF-\u0026alpha;), in kidney homogenate were measured using a sandwich enzyme-linked immunoassay kits specific to each cytokine (R\u0026amp;D system, USA). The measurements were performed at 450 nm using a microplate-reading spectrophotometer (Thermo Scientific Multiskan FC). The levels of TNF-\u0026alpha;, IL-1\u0026beta; and IL-6 were expressed as pg/mg of protein (El Gamal et al. 2014).\u003c/p\u003e\n\u003cp\u003eFor histological analysis, the second kidney was fixed in 10 % formalin for 7 days and further paraffin embedded. Sections of 4-5 \u0026mu;m were made and further stained with hematoxylin and eosin (H\u0026amp;E). The section were examined with light microscope (Ziess Axioscope), digital camera and Minisee software were used for images capture.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData were expressed as mean \u0026plusmn; standard error of mean. Statistical analysis was performed using one-way analysis of Variance (ANOVA) followed by the Tukey post hoc test. \u003cem\u003eP \u003c/em\u003e\u0026lt; 0.05 was considered statistically significant. All analyses were performed using Graphpad prism software 8.01 version.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eEffect of \u003cem\u003eC. zeylanicum\u003c/em\u003e on the body weight and relative kidney weight\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGentamicin significantly (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) decreased the rat weight gain by 45.93% and increased the relative kidney weight by 48.34% as compared to normal control group. AECZ at the doses of 200 and 400 mg/kg significantly (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) prevented the decrease of weight gain and the increase of relative kidney weight by 14.13 % and 17.39 % respectively compared to gentamicin group. AECZ administered alone significantly increased the body weight gain as compared to normal control (Table I).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffects of the stem barks aqueous extract of \u003cem\u003eC. zeylanicum\u003c/em\u003e on hematological parameters\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 shows the effects of AECZ on some hematological parameters. Apart from the number of monocytes, no other hematological parameter varied significantly regardless of the treatment received. Gentamicin significantly decreased by 52.95 % (\u003cem\u003ep \u003c/em\u003e\u0026lt; 0.001) the number of monocytes compared to the normal control. Silymarin (50 mg/kg), AECZ at the doses of 200 and 400 mg/kg significantly increased the number of monocytes by 52.50 % (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05), 90 % (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) and 67.50 % (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.01) respectively, compared to the group treated only with gentamicin.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffects of the aqueous extract of \u003cem\u003eC. zeylanicum\u003c/em\u003e stem barks on serum glucose, albumin, total protein and aspartate amino-transferase\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe effect of AECZ on serum glucose, total proteins, albumin and aspartate amino-transferase (ASAT) is presented in Table 3. Consecutive to gentamicin administration, it was observed a significant decrease of proteinemia (25 %) as compare to normal control. Compared to GM group, AECZ at the doses of 200 mg/kg and 400 mg/kg significantly inhibited the decrease of proteinemia by 17.30 % (\u003cem\u003ep \u003c/em\u003e\u0026lt; 0.05) and 23.07 % (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.01), respectively. In the GM group, the serum concentration of albumin increased significantly by 15.91 % (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) compared to normal control group, but concomitant treatment with GM and AECZ at the doses of 200 and 400 mg/kg, significantly (p \u0026lt; 0.001) reduced the serum albumin by 12.83 and 13.73 respectively. The serum concentration of Aspartate amino-transferase increased significantly by 57.7 % (p\u0026lt;0.001) in GM group when compared to normal control. The administration of \u003cem\u003eC. zeylanicum \u003c/em\u003eextract at the doses of 200 and 400 mg/kg or Silymarin (50 mg/kg) resulted in a significant reduction in ASAT activity, respectively, by 52.71% (\u003cem\u003ep \u003c/em\u003e\u0026lt; 0.01), 64.70 % (\u003cem\u003ep \u003c/em\u003e\u0026lt; 0.001), and 53.38% (\u003cem\u003ep \u003c/em\u003e\u0026lt; 0.01) as compared to gentamicin intoxicated rats. None of the evaluated parameter was affected by AECZ, when administered alone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffects of the aqueous extract of \u003cem\u003eC. zeylanicum\u003c/em\u003e stem barks on some kidney biomarkers and electrolytes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe effects of AECZ on kidney\u0026rsquo;s function were evaluated by determining the rate of creatinine, uric acid, urea and electrolytes (calcium, potassium, sodium and chloride ions) in serum (Table 4). Gentamicin significantly increased serum creatinine by 77.72%, urea by 131.14%, uric acid by 123.03% and decreased calcemia by 56.56% as compared to normal control. In comparison to negative control group, the two doses of AECZ (200 mg/kg and 400\u0026nbsp;mg/kg) significantly (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) inhibited the increase of serum creatinine by 43.72% and 47.16%, urea by 57.08% and by 47.16% and uric acid by 57.08% and 47.16% respectively. AECZ at the doses of 200\u0026nbsp;mg/kg and 400 mg/kg also prevented the decrease of calcemia by 122.48% and 116.06% respectively. Likewise, Silymarin also prevented this decrease. The serum level of potassium and sodium were not significantly affected by any of the treatment as compared to normal control.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of the aqueous extract of \u003cem\u003eC. zeylanicum\u003c/em\u003e stem barks on renal oxidative stress parameters\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe effects of the aqueous extract of \u003cem\u003eC. zeylanicum \u003c/em\u003estem barks on some kidney markers of oxidative stress are shown in Figure 1. The renal activity of SOD in the negative control decreased significantly (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) by 73.79 % (10.3 \u0026plusmn; 1.14), compared with the normal control group (39.3 \u0026plusmn; 5.05). However, pretreatment with Silymarin (50 mg/kg), AECZ (200 mg/kg) and AECZ (400 mg/kg), significantly (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) enhanced superoxide dismutase concentration by about 300.97 %, 406.79 % and 377.66 % (41.30 \u0026plusmn; 4.45, 52.20 \u0026plusmn; 3.78 and 49.20 \u0026plusmn; 4.23, respectively) compared with the gentamicin group (10.30 \u0026plusmn; 1.14).\u003c/p\u003e\n\u003cp\u003eTreatment with GM induced a significant decrease (\u003cem\u003ep \u003c/em\u003e\u0026lt; 0.001) in the renal activity of CAT (68.60 \u0026plusmn; 2.89) as compared to normal control rats (168.00 \u0026plusmn; 11.00). Silymarin (50 mg/kg) significantly increased (\u003cem\u003ep \u003c/em\u003e\u0026lt; 0.001) the activity of CAT in the kidneys by 76.38 % as compared to GM group (121.00 \u0026plusmn; 12.7 vs 68.60 \u0026plusmn; 2.89). AECZ at the doses of 200 mg/kg and 400 mg/kg significantly enhanced CAT concentration in a dose-dependent manner by about 57.43% (108.00 \u0026plusmn; 3.33) and 86.58 % (128.00 \u0026plusmn; 7.91) compared to gentamicin group (68.60 \u0026plusmn; 2.89).\u003c/p\u003e\n\u003cp\u003eAn intraperitoneal injection of rats with gentamicin (100 mg/kg) for 14 days decreased the content of GSH significantly by about 70.87 % (43.40 \u0026plusmn; 5.43), compared to the normal control group (168.00 \u0026plusmn; 11.01). Moreover, pretreatment with silymarin (50 mg/kg) or AECZ 200 mg/kg and 400 mg/kg one hour before gentamicin administration, caused a significant 2.3, 3.2 and 2.94-fold increases in renal glutathione content (100.00 \u0026plusmn; 3.33; 139.00 \u0026plusmn; 10.60 and 128.01 \u0026plusmn; 7.91), respectively, compared with the gentamicin group ( 43.40 \u0026plusmn; 5.43).\u003c/p\u003e\n\u003cp\u003eGentamicin injection (100 mg/kg/day) for 14 days caused significant elevation (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.01) of renal lipid peroxidation, which manifested as an increase in malondialdehyde concentration by 1.37 fold (4.37 \u0026plusmn; 0.13), compared with the normal control group (3.19 \u0026plusmn; 0.02). Pretreatment with silymarin (50 mg/kg), AECZ (200 mg/kg) or AECZ (400 mg/kg) for 14 days before gentamicin, significantly reduced malondialdehyde concentration by about 38.58 %, 38.21 % and 37.75 % reaching (2.64 \u0026plusmn; 0.21; 2.70 \u0026plusmn; 0.33 and 2.72 \u0026plusmn; 0.14), respectively in comparison with the gentamicin group (4.37 \u0026plusmn; 0.13).\u003c/p\u003e\n\u003cp\u003eGentamicin treated rats (negative control) showed significant decrease of 27 % (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.01) in kidney protein content as compared to normal control, whereas there was a significant increase in total protein content when animals were treated with Silymarin (60.27 %, p \u0026lt; 0.001), AECZ 200 mg/kg (53.42 %, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) and AECZ 400 mg/kg (35.61 %, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.01) as compared to GM treated rats.\u003c/p\u003e\n\u003cp\u003eThe level of nitrite was increased significantly by 112.64 % (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) in gentamicin-treated rats as compared to normal rats. This concentration of nitrite was decreased significantly by 40.81 % (\u003cem\u003eP \u003c/em\u003e\u0026lt; 0.01) in Silymarin group, by 53.78 % (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) in AECZ (200 mg/kg) group and by 47.02 (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) in AECZ (400 mg/kg) group as compared to GM treated rats.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of the aqueous extract of \u003cem\u003eC. zeylanicum\u003c/em\u003e stem bark on pro-inflammatory cytokines (TNF\u0026alpha;, IL-1\u0026beta;, IL-6).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs depicted in Figure 2, when compared to normal control group, GM administration induced a significant (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) 2.21-fold elevation of TNF-𝛼 (116.0 \u0026plusmn; 6.3 to 257.0 \u0026plusmn; 18.9 pg/mg of protein). However, when this animals were concomitantly treated with Silymarin (50 mg/kg) and GM, a 1.43-fold significantly (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) decreased the TNF-𝛼 levels was noted. In groups treated with AECZ at the doses of 200 and 400 mg/kg, a 1.34-fold and a 1.70-fold decrease of the TNF-𝛼 levels were respectively observed.\u003c/p\u003e\n\u003cp\u003eGM administration induced a significant (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) 2.17-fold elevation of IL-6 (from 39.3 \u0026plusmn; 1.72 to 85.4 \u0026plusmn; 3.45 pg/mg of protein) when compared to normal control rats. As compared to the GM treated rats, Silymarin (50 mg/kg) significantly (\u003cem\u003ep \u003c/em\u003e\u0026lt; 0.001) decreased the IL-6 levels by 1.81-fold. In groups treated AECZ at the doses of 200 and 400 mg/kg, a significant (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) 1.58-fold and 1.86-fold decrease of the IL-6 level was respectively observed.\u003c/p\u003e\n\u003cp\u003eFigure 2 also shows the effects of AECZ and Silymarin on the levels of IL-1\u0026beta; in GM-treated rats induced treated rats. When Compared to normal control rats, gentamicin induced a 2.26-fold significant (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) elevation of IL-1\u0026beta; (from 22.9 \u0026plusmn; 1.31 to 51.9 \u0026plusmn; 1.6 pg/mg of protein).\u003c/p\u003e\n\u003cp\u003eAs compared to GM group, Silymarin (50 mg/kg) significantly (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) decreased the IL-1\u0026beta; levels by 1.37-fold (from 51.9 \u0026plusmn; 1.6 to 37.8\u0026plusmn; 1.85 pg/mg of protein). Treatment with AECZ at the doses of 200 and 400 mg/kg significantly decreased the level of IL-1\u0026beta; respectively by 1.40-fold (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.01) and 1.66-fold (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003eAECZ administered alone at the dose of 400 mg/kg did no significantly affect the cytokines\u0026rsquo; content although a slight increase in IL-1\u0026beta; was noted, when compared to the normal control.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffects of \u003cem\u003eC. zeylanicum \u003c/em\u003eaqueous extract on renal histology\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMicroscopically, kidney sections from control rats revealed the normal structure of renal parenchyma (Figure 3A). The kidney of rats in negative control group (Figure 3B) presented many structural alterations including leucocytes infiltration (inflammation), tubular necrosis, tubular clarification, cilia loss, glomerular degeneration, mesangial expansion and significant reduction of urinary space. The architecture of the kidney of rats treated with AECZ at the doses of 200 mg/kg and 400 mg/kg as well as Silymarin (Figures 3C, 3D and 3E respectively) showed no histopathological alterations as compared to normal control group.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe purpose of this work was to evaluate the potential nephroprotective activity of the lyophilized aqueous extract of \u003cem\u003eCinnamomum zeylanicum\u003c/em\u003e stem‑bark in gentamicin-induced nephrotoxicity. Gentamicin (GM) is a typical aminoglycoside widely used for treatment of severe gram-negative bacterial infections. Despite its enormous therapeutic benefits as an antibiotic drug, its clinical use is limited mainly because of its nephrotoxicity side effect (Ali et al. 2005). It has been estimated that up to 30% of patients treated with GM above 7 days show some signs of nephrotoxicity (Paterson et al. 1998).\u003c/p\u003e\n\u003cp\u003eRenal oxidative stress, acute tubular necrosis, glomerular damage and inflammation are some of the major events implicated in gentamicin-induced nephrotoxicity (Jose et al. 2017). In the present study, 14 days of gentamicin injection, reduced body weight gain and increased the kidney relative weight. The decrease of body weight gain could be a result of increased proteolysis, reduced proteins synthesis (Horibe et al. 2004; Adil et al. 2016; Randjelović et al. 2017). The proteolysis and reduced proteins synthesis was confirmed in this study through the decrease of the level of total proteins in the serum and kidneys of gentamicin-treated animal. Any toxic substance that triggers a good functioning of the kidney provokes an inflammatory response in the kidney tissue, as well as it hypertrophies (Witthawaskul et al. 2003; Dhodi et al. 2015); this may justify the increase of relative kidney weight observed in animal group that received gentamicin. The aqueous extract as well as Silymarin significantly improved body weight gain, prevented the decrease of the total serum proteins and the increase of kidney relative weight. Although AECZ administered alone significantly increased the body weight gain, it did not affect the protein content, rolling out a probable effect of this extract on the protein synthesis. It is therefore, more likely that it instead prevent the proteolysis.\u003c/p\u003e\n\u003cp\u003eApart from the monocyte count, which decreased in animals treated with gentamicin, no other hematological parameter varied significantly independently of the treatment. This can be justified by the relatively short duration of treatment which was not enough to be able to induce any modification of the erythropoietin content. The decrease in the number of monocytes in the blood could be explained by their migration from the blood stream to the injured tissues.\u003c/p\u003e\n\u003cp\u003eElectrolyte balance is essential for normal homeostasis. Aminoglycosides cause derangements of renal functions by accumulating on the membranes of the proximal convoluted tubule, disturbing the reabsorption and secretion of electrolytes and in that way causes homeostatic imbalance. In the present study, serum calcium was reduced significantly and a non-significant decrease in serum sodium and potassium in gentamicin treated rats were observed. These observations on serum sodium and potassium levels although non-significant, are in agreement with those of Nafiu et al. (2019) showing that serum sodium and potassium reduction were observed in gentamicin treated rats, indicative of lesions in renal tubular epithelium and despair of Na\u003csup\u003e+\u003c/sup\u003e\u0026ndash;K\u003csup\u003e+\u003c/sup\u003eATPase by gentamicin. Studies in animal and human have demonstrated that gentamicin and other aminoglycosides impair calcium transport in the renal tubules and, in some instances, result in a significant increase in urinary calcium excretion and in that way causes hypocalcemia (Randjelović et al. 2017). AECZ as well as Silymarin inhibited the decrease of calcemia in this study. This effect may be due to the antioxidative properties of AECZ which prevented the cell membranous lipids peroxidation and tubular cell necrosis.\u003c/p\u003e\n\u003cp\u003eOne of the mechanism through which gentamicin induces nephrotoxicity is by causing a significant increase, in the blood stream, of the levels of renal function markers such as creatinine, urea, uric acid, albumin and ASAT, indicating renal dysfunction (Jain and Singhai 2010; Safa et al. 2010).\u003c/p\u003e\n\u003cp\u003eAdministration of AECZ or Silymarin along with gentamicin caused significant decrease in the concentration of creatinine, urea, uric acid, albumin and ASAT while a significant increase in total protein in the serum was noted, suggesting a protective effect of AECZ or Silymarin. Similar protective studies of different extracts against gentamicin have been reported previously (El-Tantawy et al. 2013; El Gamal et al. 2014).\u003c/p\u003e\n\u003cp\u003eGentamicin generates reactive oxygen species (ROS) in the kidney. ROS are a trigger of oxidative stress, which is the gateway to inflammatory pathways. It has been reported that during inflammation, different type of cells, e.g. macrophages and neutrophils play a major role in the production of reactive oxygen species, that will create antioxidant imbalance and the peroxidation of cell components (El-Tantawy et al. 2013).\u003c/p\u003e\n\u003cp\u003eTherefore, free radicals are a critical determining factor that plays an important role in the mechanism leading to the induction of pro-inflammatory mediators. Oxidative stress is one of the major causes for emerging acute and chronic disorders. Results confirmed that after gentamicin administration, the levels of various tissue antioxidant like SOD, reduced-glutathione and catalase were decreased significantly in rats. This declined results in increasing lipid peroxidation which also play a major role in gentamicin-induced nephrotoxicicty (Jose et al. 2017). It is well established that extracts and oils obtained from \u003cem\u003eCinnamomum zeylanicum\u003c/em\u003e have strong free radical scavenging or antioxidant activity due to the presence of flavonoids, polyphenolic, and phenolic compounds in the cinnamon (Jayaprakasha et al. 2006). In the present study, AECZ or Silymarin administration reduced oxidative stress by inhibition of lipid peroxidation therefore boosted the activity of SOD, CAT and glutathione.\u003c/p\u003e\n\u003cp\u003eVasodilator effects of NO appear to play a role in GM-induced nephrotoxicity (Christo et al. 2011). In fact, NO seems to increase renal injury through its reaction with superoxide radical (O\u003csub\u003e2\u003c/sub\u003e\u003csup\u003e-\u003c/sup\u003e), generating the highly cytotoxic peroxynitrite oxidant (Koppenol et al. 1992).\u003c/p\u003e\n\u003cp\u003eGentamicin treatment induced an increase in nitric oxide levels which in turn increase inflammation that ultimately leads to cellular damage. In the present study, gentamicin treatment induced an increase in the nitric oxide level, therefore, increasing the inflammation leading to cellular damage. The AECZ or Silymarin treatment significantly attenuate nitric oxide induced oxidative stress leading to reduction in inflammation. To confirm this, the effects of AECZ or silymarin were evaluated on the levels of some pro-inflammatory markers.\u003c/p\u003e\n\u003cp\u003eThe role of various pro-inflammatory mediators such as TNF\u0026alpha;, IL-6 and IL- 1\u0026beta;, are well known in the kidney diseases (El Gamal et al. 2014; Jose et al. 2017). In this study, AECZ (200 and 400 mg/kg) or silymarin (50 mg/kg) significantly downregulates the renal proinflammatory cytokines (TNF-𝛼, IL-6 and IL- 1\u0026beta;). These findings corroborate those of earlier studies demonstrating that plant extracts are able to reverse the increasing of pro-inflammatory cytokines induced by gentamicin (Joshi et al. 2010; Erjaee et al. 2015; Jose et al. 2017). Previous study on the hydroalcoholic extract of \u003cem\u003eCinnamomum zeylanicum\u003c/em\u003e stem bark on nociception and anxiety showed that this anti-inflammatory effect is ascribed to trans-cinnamaldehyde component of Cinnamon (Chao et al. 2008; Seema and Sparsh 2019). Thus, the anti-inflammatory effect observed in this study may be due to the reduction of inflammatory mediators release.\u003c/p\u003e\n\u003cp\u003eEvidences have indicated that the renal toxicity of gentamicin is due to its selective accumulation in the renal proximal convoluted tubules which subsequently leads to the loss of the tubule brush border integrity, severe degenerationnecrosis in epithelial cells of the proximal tubules, and infiltration of mononuclear cells in intertubular spaces (Lopez-Novoa et al. 2011; Raju et al. 2011). In this study, the microscopic analysis of the kidney tissues revealed the nephrotoxic effect of gentamicin. The histological analyses of kidney sections from gentamicin-treated animals (negative control) showed inflammations, fibrosis, tubular clarifications, glomerular hypertrophy and degeneration with a reduced urinary space. Previous studies described as well these renal tissue damages induced by gentamicin (Dhodi et al. 2015; Randjelović et al. 2017). The histological analysis of kidney sections from animals treated with AECZ (200 mg/kg and 400 mg/kg) as well as Silymarin presented an aspect similar to that of normal animals. This shows that AECZ prevented the renal tissues damages of the gentamicin. This histopathological observations correlate the pathologic variations of the biochemical values. The animals that were treated with AECZ (400 mg/kg) alone showed no pathological changes. This indicates that AECZ does not possess any adverse effects. Phytochemical screening of extract revealed the presence of several active principles such as phenolic compounds, flavonoids, tannins and saponins (Mallavarapu and Rajeswara 2007). Thus, the nephroprotective effect observed in the present study might be due to the presence of these active constituents especially E-cinnamaldehyde and o-methoxy cinnamaldehyde, eugenol and cinnamic acid which are the major compounds isolated from \u003cem\u003eCinnamomum zeylanicum\u003c/em\u003e (Seema and Sparsh 2019).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAccording to the results obtained in the present study, AECZ has a potential to prevent kidney damages. AECZ protect against gentamicin induced kidney toxicity by inhibiting oxidative stress, lipid peroxidation, inflammation and thereby suppressed the pro-inflammatory cytokines such as TNF-\u0026alpha;, IL 1\u0026beta;, IL-6 and protect kidney tissues for necrosis. AECZ might be a good candidate for the development of new drugs that can protect against acute kidney diseases.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAECZ\u003cem\u003e: Cinnamomum zeylanicum \u003c/em\u003estem-bark aqueous extract\u003c/p\u003e\n\u003cp\u003eANOVA: One Way Analysis of Variance\u003c/p\u003e\n\u003cp\u003eASAT: Aspartate Amino-Transferase\u003c/p\u003e\n\u003cp\u003eCAT: Catalase\u003c/p\u003e\n\u003cp\u003eDG: glomerular degeneration.\u003c/p\u003e\n\u003cp\u003eDT: distal tubule\u003c/p\u003e\n\u003cp\u003eEDTA: Ethylenediaminetetraacetic acid\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eG: glomeruli\u003c/p\u003e\n\u003cp\u003eGM\u0026nbsp;: Gentamicin\u003c/p\u003e\n\u003cp\u003eGSH: Reduced glutathione\u003c/p\u003e\n\u003cp\u003eH\u0026amp;E: Hematoxylin and Eosin\u003c/p\u003e\n\u003cp\u003eHb: hemoglobin\u003c/p\u003e\n\u003cp\u003eHCT: hematocrit\u003c/p\u003e\n\u003cp\u003eIL: Interleukin\u003c/p\u003e\n\u003cp\u003eLI: leucocyte infiltrations\u003c/p\u003e\n\u003cp\u003eMDA: malondialdehyde\u003c/p\u003e\n\u003cp\u003eNF-𝜅B: Nuclear Factor-kappa B\u003c/p\u003e\n\u003cp\u003eNO: Nitric Oxide\u003c/p\u003e\n\u003cp\u003ePT: proximal tubule\u003c/p\u003e\n\u003cp\u003eRBC: Red Blood Cell\u003c/p\u003e\n\u003cp\u003eROS\u0026nbsp;: Reactive Oxygen Species\u003c/p\u003e\n\u003cp\u003eSEM: Standard Error of Mean\u003c/p\u003e\n\u003cp\u003eSily 50: silymarin (50\u0026nbsp;mg/kg).\u003c/p\u003e\n\u003cp\u003eSOD: superoxide dismutase\u003c/p\u003e\n\u003cp\u003eTC: tubular clarification\u003c/p\u003e\n\u003cp\u003eTNF\u0026alpha;: Tumor Necrosing Factor\u003c/p\u003e\n\u003cp\u003eUK: United Kingdom\u003c/p\u003e\n\u003cp\u003eUS: urinary space\u003c/p\u003e\n\u003cp\u003eUSA: United Stated of America\u003c/p\u003e\n\u003cp\u003eWBC: White Blood Cell\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003eAbdel-Azeem AS, Hegazy AM, Zeidan HM, et al (2017) Potential Renoprotective Effects of Rosemary and Thyme Against Gentamicin Toxicity in Rats. 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J Complement Integr Med 8:. https://doi.org/10.2202/1553-3840.1490\u003c/p\u003e\n\u003cp\u003eNyadjeu P, Nguelefack-Mbuyo EP, Atsamo AD, et al (2013) Acute and chronic antihypertensive effects of Cinnamomum zeylanicum stem bark methanol extract in L-NAME-induced hypertensive rats. BMC Complement Altern Med 13:. https://doi.org/10.1186/1472-6882-13-27\u003c/p\u003e\n\u003cp\u003ePaterson DL, Robson JMB, Wagener MM (1998) Risk factors for toxicity in elderly patients given aminoglycosides once daily. J Gen Intern Med 13:735\u0026ndash;739. https://doi.org/10.1046/j.1525-1497.1998.00224.x\u003c/p\u003e\n\u003cp\u003eRaju S, Kavimani S, Uma Maheshwara rao V, et al (2011) Floral extract of Tecoma stans: A potent inhibitor of gentamicin-induced nephrotoxicity in vivo. Asian Pac J Trop Med 4:680\u0026ndash;685. https://doi.org/10.1016/S1995-7645(11)60173-9\u003c/p\u003e\n\u003cp\u003eRandjelović P, Veljković S, Stojiljković N, et al (2017) Gentamicin nephrotoxicity in animals: Current knowledge and future perspectives. EXCLI J. 16:388\u0026ndash;399\u003c/p\u003e\n\u003cp\u003eSafa J, Argani H, Bastani B, et al (2010) Protective effect of grape seed extract on gentamicin-induced acute kidney injury. Iran J Kidney Dis 4:285\u0026ndash;291\u003c/p\u003e\n\u003cp\u003eSeema J, Sparsh G (2019) Effects of Cinnamomum zeylanicum bark extract on nociception and anxiety like behavior in mice. Asian J Pharm Clin Res 12:236\u0026ndash;241. https://doi.org/10.22159/ajpcr.2019.v12i9.31287\u003c/p\u003e\n\u003cp\u003eShaughnessy DT, Setzer RW, DeMarini DM (2001) The antimutagenic effect of vanillin and cinnamaldehyde on spontaneous mutation in Salmonella TA104 is due to a reduction in mutations at GC but not AT sites. Mutat Res - Fundam Mol Mech Mutagen 480\u0026ndash;481:55\u0026ndash;69. https://doi.org/10.1016/S0027-5107(01)00169-5\u003c/p\u003e\n\u003cp\u003eSinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389\u0026ndash;394. https://doi.org/10.1016/0003-2697(72)90132-7\u003c/p\u003e\n\u003cp\u003eSlack P (1987) Analytical methods manual, 2nd ed. Leatherhead Food Research Association, Leatherhead England\u003c/p\u003e\n\u003cp\u003eStavinoha RC, Vattem DA (2015) Potential neuroprotective effects of cinnamon. Int. J. Appl. Res. Nat. Prod. 8:24\u0026ndash;46\u003c/p\u003e\n\u003cp\u003eUllah N, Azam Khan M, Khan T, Ahmad W (2014) Protective potential of \u003cem\u003eTamarindus indica\u003c/em\u003e against gentamicin-induced nephrotoxicity. Pharm Biol 52:428\u0026ndash;434. https://doi.org/10.3109/13880209.2013.840318\u003c/p\u003e\n\u003cp\u003eUllah N, Azam Khan M, Khan T, Ahmad W (2013) Bioactive traditional plant Cinnamomum zeylanicum successfully combat against nephrotoxic effects of aminoglycosides. Bangladesh J Pharmacol 8:15\u0026ndash;21. https://doi.org/10.3329/bjp.v8i1.12862\u003c/p\u003e\n\u003cp\u003eVerspohl EJ, Bauer K, Neddermann E (2005) Antidiabetic effect of Cinnamomum cassia and Cinnamomum zeylanicum in vivo and in vitro. Phyther Res 19:203\u0026ndash;206. https://doi.org/10.1002/ptr.1643\u003c/p\u003e\n\u003cp\u003eWilbur KM, Bernheim F, Shapiro OW (1949) The thiobarbituric acid reagent as a test for the oxidation of unsaturated fatty acids by various agents. Arch Biochem Biophys 24:305\u0026ndash;313\u003c/p\u003e\n\u003cp\u003eWitthawaskul P, Panthong A, Kanjanapothi D, et al (2003) Acute and subacute toxicities of the saponin mixture isolated from Schefflera leucantha Viguier. J Ethnopharmacol 89:115\u0026ndash;121. https://doi.org/10.1016/S0378-8741(03)00273-3\u003c/p\u003e"},{"header":"Tables","content":"\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:24.0pt;line-height:150%;font-size:15px;font-family:\"Calibri\",sans-serif;text-indent:-24.0pt;'\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 11px; line-height: 150%; font-family: Verdana, Geneva, sans-serif; color: rgb(0, 0, 0);\"\u003eTable 1\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e: Effects of \u003cem\u003eC.zeylanicum\u003c/em\u003e stem bark aqueous extract on body weight and relative kidney weight\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp 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style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eBW D14\u0026nbsp;\u003c/strong\u003e(g)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border: none;background: silver;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e179.88 \u0026plusmn; 3.96\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border: none;background: silver;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e161.40 \u0026plusmn; 6.78\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border: none;background: silver;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e174.61 \u0026plusmn; 7.61\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border: none;background: silver;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e191.13 \u0026plusmn; 8.79\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border: none;background: silver;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e178.50 \u0026plusmn; 3.23\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border: none;background: silver;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e190.21 \u0026plusmn; 4.13\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 92.15pt;border: none;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u0026Delta;BW D14-D1\u0026nbsp;\u003c/strong\u003e(%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border: none;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e29.24 \u0026plusmn; 1.49\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border: none;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e15.81 \u0026plusmn; 0.48\u003csup\u003ez\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border: none;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e33.03 \u0026plusmn; 1.11\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border: none;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e39.05 \u0026plusmn; 2.64\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border: none;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e33.66 \u0026plusmn; 2.07\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border: none;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e40.51 \u0026plusmn; 1.13\u003csup\u003ez\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 92.15pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: silver;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eRelative kidney weight\u0026nbsp;\u003c/strong\u003e(g/100g BW)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: silver;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e0.62 \u0026plusmn; 0.01\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: silver;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e0.92 \u0026plusmn; 0.01\u003csup\u003eZ\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: silver;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e0.72 \u0026plusmn; 0.01\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.85pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: silver;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e0.79 \u0026plusmn; 0.01\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 70.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: silver;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e0.76 \u0026plusmn; 0.02\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: silver;padding: 0in;height: 1pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom: 0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e0.67 \u0026plusmn; 0.01\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"margin: 6pt 0in 8pt; line-height: 150%; font-size: 15px; font-family: Calibri, sans-serif; text-align: left; text-indent: 0.5in;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eEach value represents the mean \u0026plusmn; SEM. n = 6; \u003csup\u003ez\u003c/sup\u003ep \u0026lt; 0.001 significant difference as compare to normal control. \u003csup\u003ec\u003c/sup\u003ep \u0026lt; 0.001 significant difference as compare to negative control. BW = body weight,\u0026nbsp;\u003c/span\u003e\u0026Delta;BW\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;= variation of body weight, D = day, NC = normal control, GM = gentamicin, AECZ = stem barks aqueous extract of \u003cem\u003eCinnamomum zeylanicum\u003c/em\u003e, Sily 50 = silymarin (50.mg/kg).\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:justify;text-indent:.5in;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ch2 style='margin-top:0in;margin-right:0in;margin-bottom:6.0pt;margin-left:0in;line-height:115%;font-size:17px;font-family:\"Calibri Light\",sans-serif;color:#4472C4;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/h2\u003e\n\u003ch2 style='margin-top:0in;margin-right:0in;margin-bottom:6.0pt;margin-left:0in;line-height:115%;font-size:17px;font-family:\"Calibri Light\",sans-serif;color:#4472C4;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 115%; font-weight: normal;\"\u003eTableau 2:\u0026nbsp;Effects of \u003cem\u003eC. zeylanicum\u003c/em\u003e stem bark aqueous extract on some hematological\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/h2\u003e\n\u003ch2 style='margin-top:0in;margin-right:0in;margin-bottom:6.0pt;margin-left:0in;line-height:115%;font-size:17px;font-family:\"Calibri Light\",sans-serif;color:#4472C4;text-align:justify;text-indent:63.8pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 115%; font-weight: normal;\"\u003e\u0026nbsp;parameters\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/h2\u003e\n\u003ctable style=\"width:526.8pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82.1pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 105%;\"\u003eParameters\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.25pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 105%;\"\u003eNC\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.95in;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 105%;\"\u003e\u0026nbsp;GM\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 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style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.05pt;border: none;background: silver;padding: 0in 5.4pt;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 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style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 105%;\"\u003eWBC\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"line-height: 105%;\"\u003e(x\u0026nbsp;10\u003csup\u003e3\u003c/sup\u003e/\u0026mu;L)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.25pt;border: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e6.30 \u0026plusmn; 0.67\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.95in;border: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e52.6 \u0026plusmn; 0.71\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.25pt;border: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n 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style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 105%;\"\u003eGranulo\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"line-height: 105%;\"\u003e(x\u0026nbsp;10\u003csup\u003e3\u003c/sup\u003e/\u0026mu;L)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.25pt;border: none;background: silver;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan 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style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e1.56 \u0026plusmn; 0.08\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82.1pt;border: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 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style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e6.77 \u0026plusmn; 0.28\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.25pt;border: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e7.02 \u0026plusmn; 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0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e6.82 \u0026plusmn; 0.18\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.3pt;border: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e6.88 \u0026plusmn; 0.24\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82.1pt;border: none;background: silver;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 105%;\"\u003ePLT\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"line-height: 105%;\"\u003e(x 10\u003csup\u003e3\u003c/sup\u003e/\u0026mu;L)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.25pt;border: none;background: silver;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e472.6 \u0026plusmn; 7.6\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.95in;border: none;background: silver;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e466.6 \u0026plusmn; 46.6\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.25pt;border: none;background: silver;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e458.1 \u0026plusmn; 48.2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69.45pt;border: none;background: silver;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e522.8 \u0026plusmn; 48.2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.05pt;border: none;background: silver;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e457.5 \u0026plusmn; 32.1\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.3pt;border: none;background: silver;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e29.5 \u0026plusmn; 35.7\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82.1pt;border: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 105%;\"\u003eHb\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"line-height: 105%;\"\u003e(g/dL)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.25pt;border: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e13.31 \u0026plusmn; 0.18\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.95in;border: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e12.93 \u0026plusmn; 0.64\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.25pt;border: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e13.25 \u0026plusmn; 0.35\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69.45pt;border: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e13.91 \u0026plusmn; 0.20\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.05pt;border: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e12.53 \u0026plusmn; 0.51\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.3pt;border: none;padding: 0in 5.4pt;height: 14.05pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e13.01 \u0026plusmn; 0.54\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 82.1pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 15.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 105%;\"\u003eHTC\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"line-height: 105%;\"\u003e\u0026nbsp;(%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 15.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e36.41 \u0026plusmn; 1.41\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0.95in;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 15.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e34.41 \u0026plusmn;2.55\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 15.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e34.86 \u0026plusmn; 1.85\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 15.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e36.50 \u0026plusmn; 1.53\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 15.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e33.916 \u0026plusmn; 1.09\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75.3pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: silver;padding: 0in 5.4pt;height: 15.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 105%;\"\u003e35.65 \u0026plusmn; 2.35\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:150%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eEach value represents the mean \u0026plusmn; SEM. n = 6; \u003csup\u003ez\u003c/sup\u003ep \u0026lt; 0.001\u0026nbsp;significant differences as compare to normal control.\u0026nbsp;; \u003csup\u003ea\u003c/sup\u003ep \u0026lt; 0.05, \u003csup\u003eb\u003c/sup\u003eP \u0026lt; 0.01, \u003csup\u003ec\u003c/sup\u003ep \u0026lt; 0.001 significant difference compare to gentamicin group.\u0026nbsp;NC = normal control, GM: gentamicin,\u0026nbsp;AECZ: stem barks aqueous extract of \u003cem\u003eCinnamomum zeylanicum\u003c/em\u003e, Sily 50: silymarine (50 mg/kg). WBC: white blood cells, Lympho : lymphocytes, Mono : monocytes, Granulo : granulocytes, RBC : Red blood cells, Hb : hemoglobin, PLT : platelets, HTC =hematocrit.\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:49.65pt;line-height:150%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:justify;text-indent:-49.65pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:49.65pt;line-height:150%;font-size:15px;font-family:\"Calibri\",sans-serif;text-indent:-49.65pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eTable 3:\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;Effects of \u003cem\u003eC. zeylanicum\u003c/em\u003e stem bark aqueous extract on serum glucose, total proteins, albumin and aspartate amino-tranferase\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 5.1e+2pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 92.45pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eNC\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eGM\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.1pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eSily 50 +\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u0026nbsp;GM\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eAECZ 200 + GM\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.1pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eAECZ 400 + GM\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.9pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u0026nbsp; AECZ 400\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 92.45pt;border: none;background: silver;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border: none;background: silver;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border: none;background: silver;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.1pt;border: none;background: silver;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border: none;background: silver;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.1pt;border: none;background: silver;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.9pt;border: none;background: silver;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 92.45pt;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eTP\u0026nbsp;\u003c/strong\u003e(mg/dL)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e130\u0026nbsp;\u0026plusmn; 0.02\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e104\u0026nbsp;\u0026plusmn; 0.01\u003csup\u003ey\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n 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150%;\"\u003e122 \u0026plusmn; 0.01\u003csup\u003ea\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.1pt;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e128 \u0026plusmn; 0.03\u003csup\u003eb\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.9pt;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e129 \u0026plusmn; 0.04\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 92.45pt;border: none;background: silver;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eAlbumin\u0026nbsp;\u003c/strong\u003e(mg/dL)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border: none;background: silver;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;margin-bottom:6.0pt;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e57.80 \u0026plusmn; 1.05\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border: none;background: silver;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e67.00 \u0026plusmn; 1.35\u003csup\u003ez\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.1pt;border: none;background: silver;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e57.50 \u0026plusmn; 1.28\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border: none;background: silver;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e58.40 \u0026plusmn; 1.01\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.1pt;border: none;background: silver;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e57.80 \u0026plusmn; 0.84\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.9pt;border: none;background: silver;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e56.50 \u0026plusmn; 1.49\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 92.45pt;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eGlucose\u0026nbsp;\u003c/strong\u003e(mg/dL)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e71.66 \u0026plusmn; 7.04\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e68.04 \u0026plusmn; 6.84\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.1pt;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e71.99 \u0026plusmn; 6.37\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e73.60 \u0026plusmn; 7.21\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.1pt;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e67.58 \u0026plusmn; 3.63\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.9pt;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e65.73 \u0026plusmn; 6.09\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 92.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eASAT (UI)\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e172.54\u0026plusmn; 32.43\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e407.81 \u0026plusmn; 79.83\u003csup\u003ez\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.1pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;190.11 \u0026plusmn; 27.84\u003csup\u003eb\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;192.85 \u0026plusmn; 23.56\u003csup\u003eb\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71.1pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;143.99 \u0026plusmn; 20.18\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;148.94 \u0026plusmn; 7.08\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"margin: 0in 0in 0in 49.65pt; line-height: 150%; font-size: 15px; font-family: Calibri, sans-serif; text-align: left; text-indent: -49.65pt;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;Each value represents the mean \u0026plusmn; SEM. n = 6;\u0026nbsp;\u003c/span\u003e\u003csup\u003e\u003cspan style=\"line-height: 150%;\"\u003ey\u003c/span\u003e\u003c/sup\u003e\u003cspan style=\"line-height: 150%;\"\u003ep\u0026lt; 0.01, \u003csup\u003ez\u003c/sup\u003ep \u0026lt; 0,001 significant difference as compare to normal control. \u003csup\u003ea\u003c/sup\u003ep \u0026lt; 0.05, \u003csup\u003eb\u003c/sup\u003ep \u0026lt; 0.01, \u003csup\u003ec\u003c/sup\u003ep \u0026lt; 0.001 significant differences as compare to negative control. NC = normal control, GM = gentamicin, AECZ = stem barks aqueous extract of \u003cem\u003eCinnamomum zeylanicum\u003c/em\u003e, Sily 50 = silymarin (50 mg/kg),\u0026nbsp;\u003c/span\u003eTP: total proteins, ASAT = Aspatate Amino-Transferase\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:6.0pt;margin-left:0in;line-height:150%;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:justify;text-indent:35.4pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:6.0pt;margin-right:0in;margin-bottom:0in;margin-left:85.05pt;line-height:150%;font-size:15px;font-family:\"Calibri\",sans-serif;text-indent:-49.05pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eTable 4\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"line-height: 150%;\"\u003e: Effects of \u003cem\u003eC. zeylanicum\u003c/em\u003e stem bark aqueous extract on some renal function biomarkers and electrolytes\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width:109.78%;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.16%;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8%;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eNC\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; GM\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eSily 50 +\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eGM\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eAECZ 200 + GM\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.92%;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eAECZ 400 + GM\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.44%;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eAECZ 400\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.16%;border: none;background: silver;padding: 0in;height: 7.25pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8%;border: none;background: silver;padding: 0in;height: 7.25pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 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style=\"font-size: 11px;\"\u003e\u003cstrong\u003eCreatinine\u0026nbsp;\u003c/strong\u003e(mg/dL)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8%;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e0.57 \u0026plusmn; 0.02\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e1.02 \u0026plusmn; 0.09\u003csup\u003ez\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e0.35 \u0026plusmn; 0.05\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e0.57 \u0026plusmn; 0.04\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.92%;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e0.55 \u0026plusmn; 0.03\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.44%;border: none;padding: 0in;height: 0.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e0.51 \u0026plusmn; 0.05\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.16%;border: none;background: silver;padding: 0in;height: 15pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eUrea\u0026nbsp;\u003c/strong\u003e(mg/dL)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8%;border: none;background: silver;padding: 0in;height: 15pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e21.80 \u0026plusmn; 1.73\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n 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style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e21.69 \u0026plusmn; 2.31\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.44%;border: none;background: silver;padding: 0in;height: 15pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e25.13 \u0026plusmn; 2.36\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.16%;border: none;padding: 0in;height: 15pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003euric Acid\u0026nbsp;\u003c/strong\u003e(mg/dL)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8%;border: none;padding: 0in;height: 15pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e2.44 \u0026plusmn; 0.12\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border: none;padding: 0in;height: 15pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e5.45 \u0026plusmn; 0.87\u003csup\u003ez\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border: none;padding: 0in;height: 15pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e2.49 \u0026plusmn; 0.12\u003csup\u003ec\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border: none;padding: 0in;height: 15pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:normal;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e2.34 \u0026plusmn; 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rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e2.31 \u0026plusmn; 0.14\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.16%;border: none;background: silver;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eCa\u003csup\u003e2+\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003e(mg/dL)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8%;border: none;background: silver;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e4.82 \u0026plusmn; 0.50\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border: none;background: silver;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e1.94 \u0026plusmn; 0.15\u003csup\u003ey\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border: none;background: silver;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n 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style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e5.50 \u0026plusmn; 0.20\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.16%;border: none;background: silver;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eNa\u003csup\u003e+\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003e(mEq/L)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8%;border: none;background: silver;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e140.80 \u0026plusmn; 1.15\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border: none;background: silver;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e134.00 \u0026plusmn; 0.70\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border: none;background: silver;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e142.60 \u0026plusmn; 0.67\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border: none;background: silver;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e135.20 \u0026plusmn; 5.39\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.92%;border: none;background: silver;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e143.40 \u0026plusmn; 0.50\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.44%;border: none;background: silver;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e141.00 \u0026plusmn; 1.44\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.16%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e\u003cstrong\u003eCl\u003csup\u003e-\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003e(mEq/L)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e105.80 \u0026plusmn; 1.01\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e104.20 \u0026plusmn; 1.20\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e104.00 \u0026plusmn; 0.66\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.9%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e108.20 \u0026plusmn; 0.96\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.92%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e105.20 \u0026plusmn; 1.49\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.44%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in;height: 17pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;font-size:15px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 11px;\"\u003e105.00 \u0026plusmn; 1.14\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:105%;font-size:15px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"font-size: 11px; line-height: 105%; font-family: Verdana, Geneva, sans-serif; color: rgb(0, 0, 0);\"\u003eEach value represents the mean \u0026plusmn; SEM. n = 6; \u003csup\u003ey\u003c/sup\u003ep \u0026lt; 0.01, \u003csup\u003ez\u003c/sup\u003ep \u0026lt; 0.001 significant differences as compare to normal control. \u003csup\u003ea\u003c/sup\u003ep \u0026lt; 0.01, \u003csup\u003ec\u003c/sup\u003ep \u0026lt; 0.001 significant differences as compare to negative control. NC = normal control, GM = gentamicin, AECZ = stem barks aqueous extract of \u003cem\u003eCinnamomum zeylanicum\u003c/em\u003e, Sily 50 = silymarin (50 mg/kg).\u003c/span\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"gentamicin, nephrotoxicity, Cinnamomum zeylanicum, antioxidant, inflammatory markers","lastPublishedDoi":"10.21203/rs.3.rs-216572/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-216572/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eNephropathies and especially nephrotoxicity has become one of serious cause of life threatening condition, because of intensive exposure to xenobiotic either by environmental pollution or drug abuse. The present study was undertaken to assess the protective effects of Cinnamomum zeylanicum stem-bark aqueous extract (AECZ) on gentamicin-induced nephrotoxicity. AECZ was prepared by maceration in water and tested orally at the doses of 200 and 400 mg/kg/day to prevent gentamicin induced nephropathies in male Wistar rats. Gentamicin (100 mg/kg/day) was administered for 14 consecutive days by intraperitoneal route, concomitantly with AECZ or silymarin (50 mg/kg/day) used as reference drug. Animal body weight was monitored during the treatment. After the last treatment of the 14 th day, a 24h urine was collected and animals were sacrificed. Blood was collected for the evaluation of hematological and renal function biomarkers. The homogenate of one kidney was used to assess oxidative stress markers and pro-inflammatory cytokine, while the other one was fixed in formaldehyde for histopathological studies. Gentamicin decreased body weight, serum total proteins and calcemia, but increased kidneys relative weight, serum creatinine, urea and uric acid. Moreover, the levels of reduced glutathione, catalase and superoxide dismutase activities were decreased, while an increase in malondialdehyde, proinflammatory cytokines (TNFα, IL-1β, IL-6) and nitrites were observed in negative control group as compared to normal control. Histological analysis of the kidney revealed the presence of tubular necrosis, glomerular degeneration and macrophage infiltration in gentamicin treated group. All these impairment parameters were prevented by AECZ and silymarin treatments.\u003c/p\u003e\u003cp\u003eAECZ has a protective effect against gentamicin-induced nephrotoxicity. The antioxidant and anti-inflammatory potentials of this extract may highly contribute to its nephroprotective activity.\u003c/p\u003e","manuscriptTitle":"Aqueous extract from Cinnamomum zeylanicum (Lauraceae) stem-bark ameliorates gentamicin-induced nephrotoxicity in rats by modulating oxidative stress and inflammatory markers","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-02-19 00:36:20","doi":"10.21203/rs.3.rs-216572/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"81fdd812-6621-4aa2-ae2e-1f66458f292f","owner":[],"postedDate":"February 19th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":2502601,"name":"Urology \u0026 Nephrology"},{"id":2502602,"name":"Toxicology"}],"tags":[],"updatedAt":"2021-02-19T00:36:20+00:00","versionOfRecord":[],"versionCreatedAt":"2021-02-19 00:36:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-216572","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-216572","identity":"rs-216572","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}