Selenium as a Hepatoprotective Agent for Organophosphate Pesticide (Monocrotophos) Toxicity in Male Rabbits

Selenium as a Hepatoprotective Agent for Organophosphate Pesticide (Monocrotophos) Toxicity in Male Rabbits | 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 Selenium as a Hepatoprotective Agent for Organophosphate Pesticide (Monocrotophos) Toxicity in Male Rabbits Fadhl A. M. Qasem, Elias M. A. Salih, Shaif M. Kasem, Nada M. AL Hamdani This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6710706/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 Background: Monochrotophos (MCP), a widely utilized organophosphate pesticide in agriculture, is highly risky to the hepatic health of most animal species. The present study was designed to examine the hepatotoxicity of MCP on hepatic cells and the probable protective role of Selenium (Se) in male rabbits. Results: 25 normal male rabbits, weighing between 1200 and 1500 g, were randomly assigned to five groups. Group 1 served as the control, and Groups 2 to 5 received 0.1 mg/kg of MCP daily for 25 days, with Groups 3, 4, and 5 receiving 2, 4, and 8 µg/kg.b.wt of Se, respectively, in addition. The blood samples collected after treatment were analyzed for serum estimation of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), total protein (T.P), albumin (Alb), total bilirubin (T.B), and direct bilirubin (D.B). Results in this study indicated that MCP exposure considerably increased serum GPT and GOT and T.B. and D.B. levels and decreased the levels of T.P. in comparison to the control group. Conversely, results in Groups 3-5, which were treated with Se, indicated significant improvement in these factors, with levels being almost as high as in the control group. Conclusions: The findings suggest that MCP causes severe hepatotoxic effects in male rabbits, while Se plays a protective role against such toxicity. Se supplementation significantly helped in the recovery of serum biomarkers to levels close to normal, thus suggesting its efficacy as an antioxidant in mitigating the liver damage induced by pesticides. The protective effect was found to be directly proportional to the dose given as an index of the importance of dietary antioxidants in reducing the health risks with pesticide exposure. Further research is warranted to explore mechanisms of the Se protective effects and their relevance to human health. Monochrotophos Selenium Antioxidant Hepatotoxicity Background The use of pesticides and the resulting pollution is one of the most important and prominent problems of our time. Although using pesticides was an urgent necessity to protect agricultural crops from pests, as well as for good quality, speed up, and increase crop production, on the other hand, it might have affected the environment, which is represented in environmental pollution and health effects due to exposure to the toxic residues of these pesticides on human, animal, and plant tissues (White, 1995 ; Riebeiro et al. , 2003 ; Allison and Heather,2019 ). The study of pesticides and their effects has occupied a large space in the research aspect and has become of interest to many research centers and laboratories in an attempt to reveal their dangers and to find alternatives that have less impact on the environment, humans, and animals ( Zera et al. , 2017 ). Organophosphate (OP) pesticides are considered to be one of the most important factors leading to environmental pollution and damage to living organisms, especially when they are used indiscriminately ( Iwan and Joiok, 2013 ). The problem of pesticide usage was further exacerbated in developing countries due to improper use of pesticides and absence of awareness ( Allison and Heather,2019 ). OPs make up about 90% of chemical pesticides, and they have been developed throughout the century ( Iwan and Joiok,2013 ; Zera et al. , 2017 ). Yemen is one of the developing countries that widely used pesticides in qat cultivation (AL-Haj et al., 2005 ; AL-Dhamari, 2007 ). The toxic effect of pesticides on humans' and animals' health was not discovered until 1932, when the World Health Organization classified OPs pesticides as highly toxic pesticides ( Goel and Aggarwal, 2007; Slimen et al. , 2018 ). Anugya et al. ( 2009 ) proved the toxicity of OP pesticides, as acute and chronic exposure to CPF pesticide caused an increase in free radicals such as H₂O₂, NO₂⁻, and NO₃⁻ in the brain and liver of mice. These pesticides were considered to generate free radicals that adversely affect the cell membranes (Hazarika et al., 2003 ; Sameeh et al., 2009 ). The toxic effect of OPs is mainly represented in their ability to inhibit the activity of AchE, the enzyme that activates the neurotransmitter Ach, which is the messenger between different parts of the parasympathetic nervous system (Gennaro et al., 2007 ; Hector et al., 2008 ; Iwan and Joiok,2013 ). Monochrotophos (MCP) is considered to be one of the most widely used OP pesticides. Indiscriminate use of OPs pesticides affects the environment, plants, animals, and human health (AL-Dhamari, 2007 ; Joshi et al., 2018 ; Kavita,2019 ; Ravneet and Dinesh,2019; Vinay et al. , 2021 ; Suman et al. , 2019 ). It has been reported that within the body cells there was a protective system of cellular protective antioxidant enzymes (CPAE), which has the ability, within certain limits, to protect cells from the harmful effects of free radicals. However, the increase of these radicals in the body of the organism might limit or reduce and inhibit the effectiveness of the activity of these protective enzymes (Salih and Muqbil, 2009 ; Gupta et al. , 2018 ). Some studies have revealed that there were compounds and chemical elements that limited the effect of these free radicals and thus protected cells from their harmful effects by scavenging these radicals before they reached the cell membrane and nullifying their effect. These compounds and chemical elements are known as antioxidants ( Vidyasagar et al. , 2004; Salih and Muqbil,2009 ; Vinay et al. , 2021 ). It has been reported that vitamins A, C, and E, as well as the elements Se and Zn, have the ability to strengthen the protective systems of cells through their activation of CPAE, in addition to acting as an inhibitor for the formation of free radicals, as they were considered to be antioxidants ( Halliwell and Gatteridag,1985 ; Ambali et al., 2007 ; Vinay et al. , 2021). Several studies indicated that Se is one of the chemical antioxidant elements and prevents the formation of free radicals in the body, which might indicate that it has a great protective effect within the body to prevent many diseases and activates CPAE inside the cells. Thus, in turn might reduce the effect of free radicals resulting from the decomposition of pesticides ( Schwaz and Fotz,1957 ). Kryukov et al. ( 2003 ) reported that Se was also included in the synthesis of selenoproteins, which form the CPAE, such as GSH, SOD, CAT, and GPx. Hence, the present study was aimed at studying the protective role of Se against the toxic effects of MCP on the liver of male rabbits. Materials and Methods Experimental animals : Twenty-five male rabbits were used in this study. Animals weighing between 1200 and 1500 g, they were purchased from the center of Al-Dhalea Governorate. They were housed in cages (60 cm high, 100 cm wide, and 100 cm long) containing husk as the bedding material and had ad libitum access to water and food. The whole experiment was carried out at the same environmental conditions under a 12 h light and 12 h dark schedule. Animals were kept for a period of 25 days for adaptations before the commencement of the experiment and divided into five groups (5 animals each) and administered orally for 25 days as follows: The first group (G1): Rabbits were given a daily oral dose of 5 ml of normal saline (served as a negative control group). The second group (G2): Rabbits were given a daily oral dose of 0.1 mg/kg bw of MCP dissolved in 1 ml of distilled water (served as a positive control group). The third group (G3): Rabbits were given a daily oral dose of 0.1 mg/kg bw of MCP dissolved in 1 ml of distilledr + 2 µg/kg bw of Se dissolved in 2 ml of distilled water. Fourth group (G4): Rabbits were given a daily oral dose of 0.1 mg/kg bw of MCP dissolved in 1 ml of distilled water + 4 µg/kg bw of Se dissolved in 4 ml of distilled water. Fifth group (G5): Rabbits were given a daily oral dose of 0.1 mg/kg bw of MCP dissolved in 1 ml of distilledr + 8 µg/kg bw of Se dissolved in 8 ml of distilled water. On the last day of the experiment, rabbits were fasted all night, then they were slaughtered in the morning, and blood samples were collected for the biochemical analysis. Animal Ethics Statement The experimental procedures using animal subjects were carried out in line with existing ethical principles informing the care and use of laboratory animals. The research had the backing of the appropriate institutional ethics committee and, therefore, adhered to all the animal protection laws during the course of the study. Aesthetic procedures were used to reduce the suffering of animals and to use the least number of animals required for obtaining credible scientific findings. Biochemical Parameters Assay The activities of serum (GPT and GOT) were assayed by the method as described by Reitman and Frankel ( 1957 ) . Serum Alb was estimated according to the methods of Doumas et al. (1971), and T.P. in the serum was measured according to the methods of Gornal et al,(1949). Serum T.B. and D.B. were determined by the colorimetric method, which was described by Tietz,(1976 ) . Using kits purchased from Biodiagnostic Company, Dokki, Giza, Egypt. Monocrotophos : The pesticide was obtained from the Agriculture Office in Al-Dhalea Governorate, where we obtained a can of 100 ml with a concentration of an active substance of 40%. The pesticide was prepared as follows: 0.25 ml of Novacron was added to 1 liter of distilled water so that this solution contains 100 mg of the active substance MCP, and therefore, every 1 ml of the solution contains 0.1 mg of the active substance MCP. Selenium A box of the selenium supplement (as Selevyte is manufactured by Vitane Pharma , USA). It contains 200 mcg of selenium per softgel and was purchased from the pharmacy of Al-Thawra Hospital, Sana'a, Yemen. The box contains 30 tablets; each tablet contains 200 µg of Se. The solution was prepared by dissolving each tablet in 200 ml of distilled water so that each 1 ml of water contains 1µg of Se. Statistical analysis The mean values of each parameter were computed considering data from 5 rabbits per group and expressed as mean ± S.D. One-way analysis of variance ( ANOVA ) followed by Duncan’s new multiple range test (DMRT) was used to determine significant differences among mean values. Mean values are judged significantly different if P ≤ 0.05. Results and discussion Serum enzymes such as ALP, GOT, GPT, total protein, albumin, and LDH are used as a means of assessing liver damage and toxicity (Kammon et al., 2010 ). GOT and GPT are important and necessary enzymes in biological processes, as they are found in high proportions in the liver; the increase in their levels in serum indicates tissue damage that might have resulted in the leakage of these enzymes in the liver ( Chatterjea and Shinde,2005 ; Guyton and Hall,2006 ). Blood circulation, ALP, and LDH are not less important than the previous two enzymes, as they are responsible for detoxification, metabolic processes, and the energetic structure of various basic functions ( Ismail and Huseyin,2008 ). In the present study, it has been reported that treatment with MCP pesticide (0.1 mg/kg b.wt.) in rabbits showed a significant increase in serum level of GPT (133.2 U/L) with a percentage of 474% increase when compared to that of the control group (23.2 U/L) and GOT (118 U/L) with an increase percentage of 375.8% when compared to that of the control group (24.2 U/L), which indicates the severe toxic effect of MCP pesticide on the rabbits of this group, as shown in Table 1. This result might be attributed to the increase in the permeability of the cell membrane that leads to the release of transaminases into the bloodstream because of the degeneration and necrosis of hepatocytes, which might be attributed to ROS induced by MCP. Our findings are consistent with the findings of other studies carried out on the toxic effect of MCP (Azmi et al., 2006 ; Rao et al. , 2006; Shweta et al. , 2007; Dwividi et al. , 2010; Begum andi, 2011a, b ; Kumar et al., 2018 ; Kavita, 2019 ). Our results are also in agreement with other studies carried out on the effect of different OP pesticides on such enzymes, viz. Petkove and Jordanove ,( 1980 ), Adilaxamamm and Reddy ,( 1995 ), Goel et al. , ( 1999 ), Possamai et al., ( 2007 ), Amirali et al , ( 2011 ), and Latrash ., ( 2011 ). Several studies confirmed that OP pesticides, including MCP, inhibit the activity of CPAE, which plays an active role in protecting the cell from various toxic effects whatsoever. The pesticides do this by accelerating the processes of LPO that create free radicals, thus raising the rate of TBARS, which is the oxidizing of free radicals of membrane lipids. Cells have destroyed the most important pillars of the durability of the cellular membrane, which means that the cytoplasm exits from its natural surroundings to the outside of the cell, which means its death (Sutcu et al., 2006 ; Kalapos et al. , 2008; Mogda et al., 2009 ). Table (1): Effect of Se (2, 4 and 8µg/kg.b.wt) against the toxic effect of MCP (0.1mg/kg.b.wt) on liver function parameters (GPT, GOT, T.P, Alb, T.B and D.B) in male rabbits GPT U/L GOT U/L Total protein g/dl Albumin. g/dl Total bilirubin mg/dl Direct bilirubin mg/dl G1 23.2 ± 0.836 24.8 ± 0.836 6.48 ± 0.083 4.18 ± 0.130 1.018 ± 0.046 0.23 ± 0.011 G2 133.2 ± 1.303* 118 ± 1.140* 6.38 ± 0.130 NS 4.52 ± 0.083 NS 1.64 ± 0.270* 0.63 ± 0.007* G3 98.6 ± 1.140* ° 91.2 ± 1.303* ° 6.48 ± 0.083* ° 4.4 ± 0.083* ° 1.4 ± 0.1* ° 0.30 ± 0.008* ° G4 81.8 ± 1.303* ° 84.6 ± 1.140* ° 6.42 ± 0.083* ° 4.32 ± .130* ° 1.12 ± 0.083* ° 0.29 ± 0.008* ° G5 68.8 ± 0.836* ° 64.6 ± 1.341* ° 6.52 ± 0.083* ° 4.06 ± 0.89* ° 1.08 ± 0.083* ° 0.27 ± 0.008* ° Mean values in each column were compared by one way ANOVA followed by Duncan’s new multiple range test. NS: Non- significant value when compared to the control group. * P ≥ 0.05 (Significant difference with respect to the control group). ° P ≥ 0.05 (Significant difference with respect to PCM-treated group). G1 = Control group, G2 = MCP group (0.1 mg/kg bw), G3= (0.1mg MCP + 2 µg/kg bw Se), G4= (0.1mg MCP + 4 µg/kg bw Se), (G5= (0.1mgMCP + 8 µg/kg bw This study showed that animals of the last three groups (G3, G4, and G5) that were treated with different doses of Se (2, 4, and 8 µg/kg bw) along with the pesticide MCP (0.1 mg/kg bw) caused a significant increase in serum enzyme levels of GPT and GOT in each group (G3, G4, and G5), which was dose-dependent on Se. The increase percentages of GPT serum levels were 25.9%, 38.5%, and 48.3%, respectively, and GOT levels were 22.7%, 28.3%, and 45.3%, respectively, when compared to the control group (G1). On the other side, when comparing the results with the MCP-treated group (G2), serum enzyme levels of GPT and GOT of each group (G3, G4, and G5) showed a significant decrease by a percentage of 26.39%, 39%, and 48% for GPT and 23%, 27%, and 46% for GOT; the decrease in GPT and GOT serum levels in each group was dose-dependent. These results were in agreement with the results of ALDesoky et al. ( 2012 ), who observed that treatment with malathion (MTN ) supplemented with Se in mice decreased serum enzyme levels of GPT and GOT when compared to mice treated with this pesticide only, which showed a significant increase in such serum enzyme levels. It has been reported that any element or chemical with antioxidant properties can (albeit partially) neutralize the toxic effects of the above-mentioned pesticides by enhancing CPAE resistance and helping to neutralize these effects before they reach the cellular protective barrier, which means that it combines with free radicals. Which pesticide creates or prevents these effects from reaching that effectiveness or effect in the absence of it ( Halliwell and Gutteridge,1985 ), and these antioxidants include vitamins A, C, and E, as well as the element Se ( Hafez, 2009; AL-Othman et al. , 2011; Aboul-Soud et al. , 2011; AL-Awthan et al. , 2012 ). In this study, the results of the indicators in the last three groups (G3, G4, and G5) indicated that treatment with Se showed a protective effect against the toxicity of MCP, although this effect was not complete, as the three different doses of Se were not enough to nullify the toxic effect of MCP, but the dose-dependent effect caused by Se confirmed its protective role as an antioxidant even when it is given in lower doses. The results of the present study were in agreement with the results of ELDesoky et al. ( 2012 ), who reported that Se had a protective effect against the toxicity of malathion MTN in mice. As a follow-up to our examinations and related statistical analyses, through which we would like to identify the extent to which liver cells are damaged or not affected by MCP pesticide, our results showed that serum levels of albumin and total protein of G2, which was treated with MCP, did not show any significant difference when compared to the control group, as shown in Table 1. These results were in agreement with the findings of Mogda et al. ( 2009 ), who studied the effect of MCP in mice, and some other studies, viz., Amirali et al. ( 2011 ), EL-Said et al. ( 1999 ), and Larsh ( 2011) , that studied the effect of OP pesticides on experimental animals. Besides those of groups (3), (4), and (5) that were given different doses of Se in addition to MCP, they did not show any significant difference in serum levels of albumin and total protein from those of G1 and G2 groups, which might be due to the fact that the MCP dose was not enough to affect the targeted cells that produced albumin and total protein. Table (1) also showed that either serum levels of total bilirubin or direct bilirubin were affected following treatment with MCP in G (2), as it showed a highly significant increase in total bilirubin or direct bilirubin levels when compared to the control group, with percentage increases of 61% and 173%, respectively. Our results were in agreement with the studies of Kumar et al. ( 2018 ) and Patel et al. ( 2012 ) that reported that MCP had a toxic effect on the liver of male rabbits. The increase in serum levels of total bilirubin or direct bilirubin following treatment with MCP might be attributed to the fact that either the bile ducts of the liver or the bile duct that leads to the duodenum were blocked and/or it might be due to an abnormal (pathological) increase in RBCs, or it might be due to the fact that the hepatocytes failed to perform their functions regarding protein metabolism ( Chatterjea and Shinde,2005 ; Guyton and Hall,2006 ). With regard to the animals of groups 3, 4, and 5, they were treated with MCP and three different doses of Se. The mean serum levels of T.B and D.B of each group showed non-significant difference when compared to the control group and a significant decrease which was dose dependent with a percentage decrease of 14%, 32%,34% respectively for T.B serum levels and 52%, 54%, 57% respectively for D.B serum levels when compared to MCP group (G2) which might be attributed to the antioxidant effect of Se in G1, G2 and G3 against the induced toxic effect of MCP in such groups which was dose dependent as the dose of Se increased the antioxidant effect against MCP toxicity decreased which agreed with finding of ALDesoky et al. ,( 2012 ) who reported that Se had a protective role against the toxic effect of malathion pesticides on the liver cells of rats. Hence, we conclude from this study that Se had a protective effect against the hepatotoxicity of MCP pesticide in rabbits. Conclusion This study confirms that Se completely counteracts MCP-induced hepatotoxicity in male rabbits in a dose-dependent fashion. MCP exposure elevated the activities of liver enzymes (GPT, GOT) and bilirubin, indicating severe hepatic injury. Se supplementation, however, effectively reduced these toxic impacts, with the highest dose (8 µg/kg b.wt) providing the highest protection. The findings suggest Se antioxidant and hepatoprotective activity against organophosphate pesticide toxicity. Further studies need to be conducted to further characterize its molecular mechanisms and therapeutic applications. This study emphasizes the importance of dietary antioxidants as preventive measures against pesticide-induced health risks and the need for greater regulation of pesticides. Abbreviations Alb Albumin ALT Alanine Aminotransferase AST Aspartate Aminotransferase CAT Catalase CPAE Cellular Protective Antioxidant Enzymes D.B Direct Bilirubin GOT Glutamate Oxaloacetate Transaminase GPT Glutamate Pyruvate Transaminase GPX Glutathio Peroxidase GSH Glutathion H 2 O 2 Hydrogen Peroxide LDH Lactate Dehydrogenase LPO Lipid Peroxidation MCP Monochrotophos MTN Malathion NS Non-Significant NO 2 − Nitrit NO 3 − Nitrate Ops Organophosphates ROS Reactive Oxygen Species Se Selenium SOD Superoxide Dismutase T.B Total Bilirubin T.P Total Protein Declarations Ethics Approval and Consent to Participate : The experimental procedures involved in the animal-subject experiments were undertaken as per ethical regulations regarding the care and use of laboratory animals. Approval to carry out the study was obtained from the concerned institutional ethics committee, thereby confirming adherence to all relevant animal welfare acts. Every attempt was made to reduce the discomfort of animals, and the fewest number of animals necessary were used to achieve valid scientific data. Approval to participate in this study was gained by following the ethical stipulations and protocols prescribed by the institution. Authorization for Dissemination : Authors involved in this research provide consent for publication of the research work in an academic journal. They confirm that all the co-authors have read the manuscript and agree to the data and the conclusions drawn. There are no interests which will compromise the integrity of the study, and all the required approvals have been taken for including the material from third party in the publication. Materials and information are available : The data sets and data considered during the current study are available from the corresponding author upon reasonable request. All data that are important to support the findings of the present study are included in the manuscript. Any supplementary information or materials can be made available when required for future studies. Conflicting Interests: The authors declare that they have no competing interests in this study. There are no financial, personal, or professional relationships that would affect the research or conclusions of the study.. Funding: No specific funding was obtained for this study. Authors' Contributions: FAMQ : Conceptualization, methodology, investigation, data collection, analysis and writing of the original draft. EMAS : Oversight, review, and editing of the manuscript. SMK : Data curation and formal analysis. NMA : Manuscript revision, validation, and visualization. Acknowledgments: The authors would like to offer their sincere thanks to the research team for their commitment and cooperation during the course of this research. We also want to thank Springer Nature and The Journal of Basic and Applied Zoology for their assistance during the publication process. 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Hazarika A, Sarkar S.N, Hajar S, Kataria M, and Malik J.(2003) .Influnce of malathion pretreatment and the toxicity of anilofos in male rats : biochemical interaction study . J. Toxicol,185;1-8. Hector C. Catan˜o , Elizabeth Carranza , Carlos Huamanı´ , Antonio F. Herna´ndez.(2008). Plasma Cholinesterase Levels and Health Symptoms in Peruvian Farm Workers Exposed to Organophosphate Pesticides. Arch Environ Contam Toxicol 55:153–159. Ismail C and Huseyin S. (2008) .The hematological effects of methyl parathion in rats. J Hazard. Mater,153:1117–1121 . Ismail Iand Ismail C. (2008). Acute effects of methyl parathion and diazinon asinducers for oxidative stress on certain biomarkers in various tissues of rainbowtrout (Oncorhynchus mykiss). Pest. Biochem .Physios,92:38–42. Iwan Desimal AND Jojok Mukono . ( 2013 ) . The effects of organophosphate pesticides exposure to liver function and cholinesterase serum activity among apple growers applying pesticides. The Indonesian Journal of Public Health ,10(1):70 – 76 . Joshi, Raju Nagaraju, Padmanabhan Sharda Rajini.(2018). Metabolic Dyshomeostasis in Rats Administered a Single dose of Monocrotophos is not Associated with Oxidative Damage in Liver and Kidney. Apurva Kumar Ramesh , 4(1):1280-1287. Kalapos M.P.(2008). The tandem of free radicals and methyglyoxal . Chemico. Biol.Inter. 171(3) ; 251-271. Kammon AM, Brar RS, Banga HS and Sodhi, S. (2010). Patho-biochemical studies on hepatotoxicity and nephrotoxicity on exposure to chlorpyrifos and Imidacloprid in layer chickens. Vet. Arhiv. 80 (5): 663- 672. Karaoz E ,Gulteken F, akdogan M, Oncu M and Gokcimen A.(2002) . Protective role of melatonin and acombintion of vitamins C & Eon lung toxicity induced by Chlorpyrifos in rats . Exp. Toxicol. Pathol. 54(2);97-108. Kavita Arora.(2017). Effects of monocrotophos (an organophosphate) on ultra-structure and SDH of liver; AChE, glucose and bilirubin in blood of rat. Journal of Entomology and Zoology Studies, 5(6): 02-06. Kavita Arora.(2019). Effect of monocrotophos (an organophosphate) on liver of albino rat – Histochemical and biochemical studies. Journal of Pharmacognosy and Phytochemistry, SP4: 95-97 Kerem, Mustafa, Nurdan BED.RL, Neslihan GURBUZ.Ozgur E K N C ,Abdulkadir BED.RL, Taylan AKKAYA ,Omer f I, AKRAK. (2007). Effects of Acute Fenthion toxicity on liver and kidney function and histology in rats. Turk .J. Med. Sci. 37 (5); 281-288. Kossmann S, Magner-Krezel Z, Sobieraj R and Szwed Z.(1997) .The assessment of nephrotoxic effect based on the determination of the activity of some selected enzymes in urine . Przegel.lek.54.(10);707-711. Kryukov G.V , Castellano S , Novoselov S.V , Lobanov A.V , Zehtab O , Guigó R , Gladyshev V.N .(2003). Characterization of mammalian selenoproteomes. Sci. 300(5624):1439-1443. Kumar V, Basniwal PK, Vijayaraghavan R.(2018). Effects of combined exposure to dichlorvos and monocrotophos on hepatotoxicity in rats. Bulletin of Pharmaceutical Research.8(1):153. Lengyl Z,Fazakas Z and Negymajteny L.(2005). Chang in the CNS of rats treated with Dimethoate in combination with other neurotoxicants in different phases of ontogenesis. Arh.Hig. Rada.Toxicol .56;257-264. Mogda K. Mansour, Afaf A.I. El-Kashoury ,M.A.Rashed and K.M.Koretem .(2009) . Oxidative and biochemical alterations induced by profenofos insecticide in rats. Nat.Sci.7(2);1-15. Narra MR , Begum G , Rajender K , Rao JV .(2011) . In vivo impact of monocrotophos on biochemical parameters of a freshwater fish during subacute toxicity and following cessation of exposure to the insecticide . Z Naturforsch C. 66(9-10):507-514. Patel A. B , Dewan A , Kaji B. C .(2012). Monocrotophos poisoning through contaminated millet flour. Arh. Hig. Rada. Toksikol 63 (3) :377-383. Petkove V. and Jordanove J. U.(1980). Enzyme hanes at chronic exposure to pesticides . proble .Hig.5;133.(in Bulgarian) . Possamai F.P, Fortunato J.J, Feier G, Agostinho, F.R, Quevedo J, Wilhelm Filho D, Dal-Pizzol F.(2007). Oxidative stress after acute and sub-chronic malathion intoxication in Wistar rats. Enviro. Toxicol.Pharmacol. 23;198–204. Rao J.V .(2006). Biochemical alterations in euryhaline fish, Oreochromis mossambicus exposed to sub-lethal concentrations of an organophosphorus insecticide, monocrotophos. Chemospher . 65(10);1814-1820. Ravneet Kaur & Dinesh Goyal . (2019) . Toxicity and degradation of the insecticide monocrotophos. Environmental Chemistry Letters , 17:1299–1324. Reitman, S. and Frankel, S.(1957): A colorimetric method for glutamic-pyruvate transaminase. Am.J.Clin.Path.28:56-68. Reza R, Mohammad A, Karami M, Ahmad A, Hamid.(2017). Adverse effects of organophosphorus pesticides on the liver: a brief summary of four decades of research Somayyeh. rh Hig Rada Toksikol,68:261-275 . Rieberio B .M, Guedes R.N, Oliveira E.E, and Santos .J.P .(2003). Insecticides resistance and synergism in Brazilian population of Sitophillus Zeamais (Coleoptera Curculionida ) . J. stored .Prod.Res.(39); 21-31. Salih E.M.A and Muqbil S.A .(2009). The Protection effect of vitamin A,C&E against the potential toxicity of Methidathion on blood factors in mail rabbits . yem.J.Biol.Sci.5(1);133-136 . Salih, Ilias M.A,EL-Eryani M.A and AL-Awar, M.S .(2011). Investigation of possible toxic effects of Methidathion and Chlorpyrifos on the liver of male rabbits . J.Nat and Appl.Sec.Vol.15 (2);537-542. Salih,E.M.A.(2010). Toxic Effect of Dimethoate and Diazinon on the Biochemical and Hematological in Male Rabbits. JJBS.vol3.(2);1-6. Sameeh A. M and Abdel-Tawab H Mossa. (2009). Lipid peroxidation and oxidative stress in rat erythrocytes induced by chlorpyrifos and the protective effect of zinc. Pest. Biochem. Physios. 93; 34–39 . Sameeh, A. M and Abdel-Tawab H. M.(2010) .Oxidative damage, biochemical and histopathological alterations in rats exposed to chlorpyrifos and the antioxidant role of zinc. Pest. Biochem.Physios. 96 ;14–23. Shweta Agrahari, Kashev C. Pandey and Krishna Gopal .(2007). Biochemical alteration induced by monocrotophos in the blood plasma of fish, Channa punctatus (Bloch) Original Research Article. Pesti. Biochem. Physios. 88 (3); 268-272. Slimen Selmi ; Kais Rtibi ; Dhekra Grami ; Hichem Sebai ; Lamjed Marzouki .(2018). Malathion, an organophosphate insecticide, provokes metabolic, histopathologic and molecular disorders in liver and kidney in prepubertal male mice. Toxicology Reports , 5 ,:189-195 . Suman Devi, Jagjeet Singh, Vijay Kumar, Vinay Malik.( 2019 ). Monocrotophos induced Biochemical and Histopathological alterations in the Kidney tissues of Mice, Chem. Biol. Lett, 6(2):39‐45. Sutcu R, Altuntas I, Yildirim B, karahan N,Demirin H and Delibas N.(2006). The effect of subchronic methidathion toxicity on rats liver: role of antioxidant vitamins C&E. Cell Biol.Toxicol.22(3);221-227. Tietz, N.W.(1976). Biuret method for the determination of total protein in serum In: Fundamental of clinical chemistry.WBS Saunders Co. Philadelphi, Toronto, London p.503 and p.879. Vidyasagsr J,Karunakar n, Reddy M.S, Rajnarayana K, Surender T and Krishna D .(2004). Oxidative stress and antioxidant status in acute organophosphorus insecticide poisoning .indi.J. Pharmacol.36 ;76-79. Vinay Malik , Jagjeet Singh , Amit Kumar & Vijay Kumar . (2021) . Protective effect of coenzyme Q10 nanoparticles against monocrotophos induced oxidative stress in kidney tissues of rats. Biologia , 76:1849–1857. White N.(1995). Insect .Mites and insecticides in stored grain ecosystem in :stored grain ecosystem . New-york.USA.123-168. Yavuz T, Altuntas I, Delibas N, Yildirim B, Candir O, Corâ A, Karahan N, Ibrisim E, Kutsal A.(2004). Cardiotoxicity in rats induced by methidathion and ameliorating effect of vitamins E and C. Hum Exp Toxicol.Jul;23(7):323-9. doi: 10.1191/0960327104ht456oa. PMID: 15311849. Additional Declarations No competing interests reported. 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-6710706","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":465999985,"identity":"61631b20-a4fc-46ee-a3f2-31d5ad5c218c","order_by":0,"name":"Fadhl A. M. Qasem","email":"data:image/png;base64,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","orcid":"","institution":"Aden University","correspondingAuthor":true,"prefix":"","firstName":"Fadhl","middleName":"A. M.","lastName":"Qasem","suffix":""},{"id":465999987,"identity":"2fabf148-5748-4fe4-b414-2efad7c1a862","order_by":1,"name":"Elias M. A. Salih","email":"","orcid":"","institution":"Aden University","correspondingAuthor":false,"prefix":"","firstName":"Elias","middleName":"M. A.","lastName":"Salih","suffix":""},{"id":465999988,"identity":"3b9126fb-b437-449d-b223-f2284a0688ac","order_by":2,"name":"Shaif M. Kasem","email":"","orcid":"","institution":"Aden University","correspondingAuthor":false,"prefix":"","firstName":"Shaif","middleName":"M.","lastName":"Kasem","suffix":""},{"id":465999989,"identity":"5d054d67-2def-4901-979c-2d7481712e25","order_by":3,"name":"Nada M. AL Hamdani","email":"","orcid":"","institution":"Sana’a University","correspondingAuthor":false,"prefix":"","firstName":"Nada","middleName":"M. AL","lastName":"Hamdani","suffix":""}],"badges":[],"createdAt":"2025-05-20 20:23:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6710706/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6710706/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90228016,"identity":"d8f7a056-b296-4505-80f8-2343abc07313","added_by":"auto","created_at":"2025-08-30 12:31:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2838719,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6710706/v1/cd5833c4-caa1-4ef2-b470-21d257158fdf.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Selenium as a Hepatoprotective Agent for Organophosphate Pesticide (Monocrotophos) Toxicity in Male Rabbits","fulltext":[{"header":"Background","content":"\u003cp\u003eThe use of pesticides and the resulting pollution is one of the most important and prominent problems of our time. Although using pesticides was an urgent necessity to protect agricultural crops from pests, as well as for good quality, speed up, and increase crop production, on the other hand, it might have affected the environment, which is represented in environmental pollution and health effects due to exposure to the toxic residues of these pesticides on human, animal, and plant tissues (White, \u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e1995\u003c/span\u003e; \u003cb\u003eRiebeiro\u003c/b\u003e \u003cb\u003eet al.\u003c/b\u003e, \u003cb\u003e2003 ; Allison and Heather,2019\u003c/b\u003e). The study of pesticides and their effects has occupied a large space in the research aspect and has become of interest to many research centers and laboratories in an attempt to reveal their dangers and to find alternatives that have less impact on the environment, humans, and animals (\u003cb\u003eZera\u003c/b\u003e \u003cb\u003eet al.\u003c/b\u003e, \u003cb\u003e2017\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eOrganophosphate (OP) pesticides are considered to be one of the most important factors leading to environmental pollution and damage to living organisms, especially when they are used indiscriminately (\u003cb\u003eIwan and Joiok, 2013\u003c/b\u003e). The problem of pesticide usage was further exacerbated in developing countries due to improper use of pesticides and absence of awareness (\u003cb\u003eAllison and Heather,2019\u003c/b\u003e). OPs make up about 90% of chemical pesticides, and they have been developed throughout the century (\u003cb\u003eIwan and Joiok,2013 ; Zera\u003c/b\u003e \u003cb\u003eet al.\u003c/b\u003e, \u003cb\u003e2017\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eYemen is one of the developing countries that widely used pesticides in qat cultivation (AL-Haj et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2005\u003c/span\u003e; AL-Dhamari, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2007\u003c/span\u003e). The toxic effect of pesticides on humans' and animals' health was not discovered until 1932, when the World Health Organization classified OPs pesticides as highly toxic pesticides (\u003cb\u003eGoel and Aggarwal, 2007; Slimen\u003c/b\u003e \u003cb\u003eet al.\u003c/b\u003e, \u003cb\u003e2018\u003c/b\u003e). Anugya et al. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2009\u003c/span\u003e) proved the toxicity of OP pesticides, as acute and chronic exposure to CPF pesticide caused an increase in free radicals such as H₂O₂, NO₂⁻, and NO₃⁻ in the brain and liver of mice. These pesticides were considered to generate free radicals that adversely affect the cell membranes (Hazarika et al., \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2003\u003c/span\u003e; Sameeh et al., \u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e2009\u003c/span\u003e). The toxic effect of OPs is mainly represented in their ability to inhibit the activity of AchE, the enzyme that activates the neurotransmitter Ach, which is the messenger between different parts of the parasympathetic nervous system (Gennaro et al., \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; Hector et al., \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2008\u003c/span\u003e; \u003cb\u003eIwan and Joiok,2013\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eMonochrotophos (MCP) is considered to be one of the most widely used OP pesticides. Indiscriminate use of OPs pesticides affects the environment, plants, animals, and human health (AL-Dhamari, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; Joshi et al., \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; \u003cb\u003eKavita,2019 ; Ravneet and Dinesh,2019; Vinay\u003c/b\u003e \u003cb\u003eet al.\u003c/b\u003e, \u003cb\u003e2021 ; Suman\u003c/b\u003e \u003cb\u003eet al.\u003c/b\u003e, \u003cb\u003e2019\u003c/b\u003e). It has been reported that within the body cells there was a protective system of cellular protective antioxidant enzymes (CPAE), which has the ability, within certain limits, to protect cells from the harmful effects of free radicals. However, the increase of these radicals in the body of the organism might limit or reduce and inhibit the effectiveness of the activity of these protective enzymes (Salih and Muqbil, \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e2009\u003c/span\u003e; \u003cb\u003eGupta\u003c/b\u003e \u003cb\u003eet al.\u003c/b\u003e, \u003cb\u003e2018\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eSome studies have revealed that there were compounds and chemical elements that limited the effect of these free radicals and thus protected cells from their harmful effects by scavenging these radicals before they reached the cell membrane and nullifying their effect. These compounds and chemical elements are known as antioxidants (\u003cb\u003eVidyasagar\u003c/b\u003e \u003cb\u003eet al.\u003c/b\u003e, \u003cb\u003e2004; Salih and Muqbil,2009 ; Vinay\u003c/b\u003e \u003cb\u003eet al.\u003c/b\u003e, \u003cb\u003e2021\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eIt has been reported that vitamins A, C, and E, as well as the elements Se and Zn, have the ability to strengthen the protective systems of cells through their activation of CPAE, in addition to acting as an inhibitor for the formation of free radicals, as they were considered to be antioxidants (\u003cb\u003eHalliwell and Gatteridag,1985 ;\u003c/b\u003e Ambali et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; \u003cb\u003eVinay\u003c/b\u003e \u003cb\u003eet al.\u003c/b\u003e, \u003cb\u003e2021).\u003c/b\u003e\u003c/p\u003e \u003cp\u003eSeveral studies indicated that Se is one of the chemical antioxidant elements and prevents the formation of free radicals in the body, which might indicate that it has a great protective effect within the body to prevent many diseases and activates CPAE inside the cells. Thus, in turn might reduce the effect of free radicals resulting from the decomposition of pesticides (\u003cb\u003eSchwaz and Fotz,1957\u003c/b\u003e). Kryukov et al. (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e2003\u003c/span\u003e) reported that Se was also included in the synthesis of selenoproteins, which form the CPAE, such as GSH, SOD, CAT, and GPx. Hence, the present study was aimed at studying the protective role of Se against the toxic effects of MCP on the liver of male rabbits.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e \u003cb\u003eExperimental animals\u003c/b\u003e: Twenty-five male rabbits were used in this study. Animals weighing between 1200 and 1500 g, they were purchased from the center of Al-Dhalea Governorate. They were housed in cages (60 cm high, 100 cm wide, and 100 cm long) containing husk as the bedding material and had \u003cem\u003ead libitum\u003c/em\u003e access to water and food. The whole experiment was carried out at the same environmental conditions under a 12 h light and 12 h dark schedule. Animals were kept for a period of 25 days for adaptations before the commencement of the experiment and divided into five groups (5 animals each) and administered orally for 25 days as follows: The first group (G1): Rabbits were given a daily oral dose of 5 ml of normal saline (served as a negative control group). The second group (G2): Rabbits were given a daily oral dose of 0.1 mg/kg bw of MCP dissolved in 1 ml of distilled water (served as a positive control group). The third group (G3): Rabbits were given a daily oral dose of 0.1 mg/kg bw of MCP dissolved in 1 ml of distilledr\u0026thinsp;+\u0026thinsp;2 \u0026micro;g/kg bw of Se dissolved in 2 ml of distilled water. Fourth group (G4): Rabbits were given a daily oral dose of 0.1 mg/kg bw of MCP dissolved in 1 ml of distilled water\u0026thinsp;+\u0026thinsp;4 \u0026micro;g/kg bw of Se dissolved in 4 ml of distilled water. Fifth group (G5): Rabbits were given a daily oral dose of 0.1 mg/kg bw of MCP dissolved in 1 ml of distilledr\u0026thinsp;+\u0026thinsp;8 \u0026micro;g/kg bw of Se dissolved in 8 ml of distilled water. On the last day of the experiment, rabbits were fasted all night, then they were slaughtered in the morning, and blood samples were collected for the biochemical analysis.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eAnimal Ethics Statement\u003c/strong\u003e \u003cp\u003e The experimental procedures using animal subjects were carried out in line with existing ethical principles informing the care and use of laboratory animals. The research had the backing of the appropriate institutional ethics committee and, therefore, adhered to all the animal protection laws during the course of the study. Aesthetic procedures were used to reduce the suffering of animals and to use the least number of animals required for obtaining credible scientific findings.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eBiochemical Parameters Assay\u003c/strong\u003e \u003cp\u003eThe activities of serum (GPT and GOT) were assayed by the method as described by Reitman and Frankel (\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e1957\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Serum Alb was estimated according to the methods of \u003cem\u003eDoumas et al. (1971), and\u003c/em\u003e T.P. in the serum was measured according to the methods of \u003cem\u003eGornal et al,(1949).\u003c/em\u003e Serum T.B. and D.B. were determined by the colorimetric method, which was described by \u003cb\u003eTietz,(1976\u003c/b\u003e\u003cem\u003e)\u003c/em\u003e. Using kits purchased from \u003cem\u003eBiodiagnostic Company, Dokki, Giza, Egypt.\u003c/em\u003e\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eMonocrotophos\u003c/b\u003e: The pesticide was obtained from the Agriculture Office in Al-Dhalea Governorate, where we obtained a can of 100 ml with a concentration of an active substance of 40%. The pesticide was prepared as follows: 0.25 ml of Novacron was added to 1 liter of distilled water so that this solution contains 100 mg of the active substance MCP, and therefore, every 1 ml of the solution contains 0.1 mg of the active substance MCP.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eSelenium\u003c/strong\u003e \u003cp\u003eA box of the selenium supplement (as \u003cb\u003eSelevyte\u003c/b\u003e is manufactured by \u003cb\u003eVitane Pharma\u003c/b\u003e, USA). \u003cem\u003eIt contains 200 mcg of selenium per softgel\u003c/em\u003e and was purchased from the pharmacy of Al-Thawra Hospital, Sana'a, Yemen. The box contains 30 tablets; each tablet contains 200 \u0026micro;g of Se. The solution was prepared by dissolving each tablet in 200 ml of distilled water so that each 1 ml of water contains 1\u0026micro;g of Se.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eStatistical analysis\u003c/strong\u003e \u003cp\u003eThe mean values of each parameter were computed considering data from 5 rabbits per group and expressed as \u003cem\u003emean\u0026thinsp;\u0026plusmn;\u003c/em\u003e\u0026thinsp;S.D. One-way analysis of variance (\u003cem\u003eANOVA\u003c/em\u003e) followed by Duncan\u0026rsquo;s new multiple range test (DMRT) was used to determine significant differences among mean values. Mean values are judged significantly different if P\u0026thinsp;\u0026le;\u0026thinsp;0.05.\u003c/p\u003e \u003c/p\u003e"},{"header":"Results and discussion","content":"\u003cp\u003eSerum enzymes such as ALP, GOT, GPT, total protein, albumin, and LDH are used as a means of assessing liver damage and toxicity (Kammon et al., \u003cspan class=\"CitationRef\"\u003e2010\u003c/span\u003e). GOT and GPT are important and necessary enzymes in biological processes, as they are found in high proportions in the liver; the increase in their levels in serum indicates tissue damage that might have resulted in the leakage of these enzymes in the liver (\u003cstrong\u003eChatterjea and Shinde,2005 ; Guyton and Hall,2006\u003c/strong\u003e). Blood circulation, ALP, and LDH are not less important than the previous two enzymes, as they are responsible for detoxification, metabolic processes, and the energetic structure of various basic functions (\u003cstrong\u003eIsmail and Huseyin,2008\u003c/strong\u003e). In the present study, it has been reported that treatment with MCP pesticide (0.1 mg/kg b.wt.) in rabbits showed a significant increase in serum level of GPT (133.2 U/L) with a percentage of 474% increase when compared to that of the control group (23.2 U/L) and GOT (118 U/L) with an increase percentage of 375.8% when compared to that of the control group (24.2 U/L), which indicates the severe toxic effect of MCP pesticide on the rabbits of this group, as shown in Table 1. This result might be attributed to the increase in the permeability of the cell membrane that leads to the release of transaminases into the bloodstream because of the degeneration and necrosis of hepatocytes, which might be attributed to ROS induced by MCP. Our findings are consistent with the findings of other studies carried out on the toxic effect of MCP (Azmi et al., \u003cspan class=\"CitationRef\"\u003e2006\u003c/span\u003e; \u003cstrong\u003eRao\u003c/strong\u003e \u003cstrong\u003eet al.\u003c/strong\u003e, \u003cstrong\u003e2006; Shweta\u003c/strong\u003e \u003cstrong\u003eet al.\u003c/strong\u003e, \u003cstrong\u003e2007; Dwividi\u003c/strong\u003e \u003cstrong\u003eet al.\u003c/strong\u003e, \u003cstrong\u003e2010; Begum andi, 2011a, b ;\u003c/strong\u003e Kumar et al., \u003cspan class=\"CitationRef\"\u003e2018\u003c/span\u003e; \u003cstrong\u003eKavita, 2019\u003c/strong\u003e). Our results are also in agreement with other studies carried out on the effect of different OP pesticides on such enzymes, viz. \u003cstrong\u003ePetkove and Jordanove\u003c/strong\u003e,(\u003cstrong\u003e1980\u003c/strong\u003e), \u003cstrong\u003eAdilaxamamm and Reddy\u003c/strong\u003e,(\u003cstrong\u003e1995\u003c/strong\u003e), \u003cstrong\u003eGoel\u003c/strong\u003e \u003cstrong\u003eet al.\u003c/strong\u003e, (\u003cstrong\u003e1999\u003c/strong\u003e), Possamai et al., (\u003cspan class=\"CitationRef\"\u003e2007\u003c/span\u003e), \u003cstrong\u003eAmirali\u003c/strong\u003e \u003cstrong\u003eet al\u003c/strong\u003e, (\u003cstrong\u003e2011\u003c/strong\u003e), and \u003cstrong\u003eLatrash\u003c/strong\u003e., (\u003cstrong\u003e2011\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eSeveral studies confirmed that OP pesticides, including MCP, inhibit the activity of CPAE, which plays an active role in protecting the cell from various toxic effects whatsoever. The pesticides do this by accelerating the processes of LPO that create free radicals, thus raising the rate of TBARS, which is the oxidizing of free radicals of membrane lipids. Cells have destroyed the most important pillars of the durability of the cellular membrane, which means that the cytoplasm exits from its natural surroundings to the outside of the cell, which means its death (Sutcu et al., \u003cspan class=\"CitationRef\"\u003e2006\u003c/span\u003e; \u003cstrong\u003eKalapos\u003c/strong\u003e \u003cstrong\u003eet al.\u003c/strong\u003e, \u003cstrong\u003e2008;\u003c/strong\u003e Mogda et al., \u003cspan class=\"CitationRef\"\u003e2009\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(1): Effect of Se (2, 4 and 8\u0026micro;g/kg.b.wt) against the toxic effect of MCP (0.1mg/kg.b.wt) on liver function parameters (GPT, GOT, T.P, Alb, T.B and D.B) in male rabbits\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Taba\" border=\"1\"\u003e\n \u003ccolgroup cols=\"7\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGPT\u003c/p\u003e\n \u003cp\u003eU/L\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGOT\u003c/p\u003e\n \u003cp\u003eU/L\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal protein\u003c/p\u003e\n \u003cp\u003eg/dl\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAlbumin.\u003c/p\u003e\n \u003cp\u003eg/dl\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal bilirubin\u003c/p\u003e\n \u003cp\u003emg/dl\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDirect bilirubin\u003c/p\u003e\n \u003cp\u003emg/dl\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e23.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.836\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e24.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.836\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e6.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.083\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e4.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.130\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.018\u0026thinsp;\u0026plusmn;\u0026thinsp;0.046\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e133.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.303*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e118\u0026thinsp;\u0026plusmn;\u0026thinsp;1.140*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e6.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.130\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003eNS\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e4.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.083\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003eNS\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.270*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.007*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e98.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.140*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e91.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.303*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e6.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.083*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.083*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.008*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e81.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.303*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e84.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.140*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e6.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.083*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e4.32\u0026thinsp;\u0026plusmn;\u0026thinsp;.130*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.083*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.008*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e68.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.836*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e64.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.341*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e6.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.083*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e4.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.083*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.008*\u003c/strong\u003e\u003cstrong\u003e\u0026deg;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eMean values in each column were compared by one way\u003c/strong\u003e \u003cstrong\u003eANOVA\u003c/strong\u003e \u003cstrong\u003efollowed by Duncan\u0026rsquo;s new multiple range test.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNS: Non- significant value when compared to the control group. * P\u0026thinsp;\u0026ge;\u0026thinsp;0.05 (Significant difference with respect to the control group). \u0026deg; P\u0026thinsp;\u0026ge;\u0026thinsp;0.05 (Significant difference with respect to PCM-treated group).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003eG1\u0026thinsp;=\u0026thinsp;Control group, G2\u0026thinsp;=\u0026thinsp;MCP group (0.1 mg/kg bw), G3= (0.1mg MCP\u0026thinsp;+\u0026thinsp;2 \u0026micro;g/kg bw Se), G4= (0.1mg MCP\u0026thinsp;+\u0026thinsp;4 \u0026micro;g/kg bw Se), (G5= (0.1mgMCP\u0026thinsp;+\u0026thinsp;8 \u0026micro;g/kg bw\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eThis study showed that animals of the last three groups (G3, G4, and G5) that were treated with different doses of Se (2, 4, and 8 \u0026micro;g/kg bw) along with the pesticide MCP (0.1 mg/kg bw) caused a significant increase in serum enzyme levels of GPT and GOT in each group (G3, G4, and G5), which was dose-dependent on Se. The increase percentages of GPT serum levels were 25.9%, 38.5%, and 48.3%, respectively, and GOT levels were 22.7%, 28.3%, and 45.3%, respectively, when compared to the control group (G1). On the other side, when comparing the results with the MCP-treated group (G2), serum enzyme levels of GPT and GOT of each group (G3, G4, and G5) showed a significant decrease by a percentage of 26.39%, 39%, and 48% for GPT and 23%, 27%, and 46% for GOT; the decrease in GPT and GOT serum levels in each group was dose-dependent. These results were in agreement with the results of \u003cstrong\u003eALDesoky\u003c/strong\u003e \u003cstrong\u003eet al.\u003c/strong\u003e (\u003cstrong\u003e2012\u003c/strong\u003e), who observed that treatment with malathion (MTN\u003cstrong\u003e)\u003c/strong\u003e supplemented with Se in mice decreased serum enzyme levels of GPT and GOT when compared to mice treated with this pesticide only, which showed a significant increase in such serum enzyme levels.\u003c/p\u003e\n\u003cp\u003eIt has been reported that any element or chemical with antioxidant properties can (albeit partially) neutralize the toxic effects of the above-mentioned pesticides by enhancing CPAE resistance and helping to neutralize these effects before they reach the cellular protective barrier, which means that it combines with free radicals. Which pesticide creates or prevents these effects from reaching that effectiveness or effect in the absence of it (\u003cstrong\u003eHalliwell and Gutteridge,1985\u003c/strong\u003e), and these antioxidants include vitamins A, C, and E, as well as the element Se (\u003cstrong\u003eHafez, 2009; AL-Othman\u003c/strong\u003e \u003cstrong\u003eet al.\u003c/strong\u003e, \u003cstrong\u003e2011; Aboul-Soud\u003c/strong\u003e \u003cstrong\u003eet al.\u003c/strong\u003e, \u003cstrong\u003e2011; AL-Awthan\u003c/strong\u003e \u003cstrong\u003eet al.\u003c/strong\u003e, \u003cstrong\u003e2012\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eIn this study, the results of the indicators in the last three groups (G3, G4, and G5) indicated that treatment with Se showed a protective effect against the toxicity of MCP, although this effect was not complete, as the three different doses of Se were not enough to nullify the toxic effect of MCP, but the dose-dependent effect caused by Se confirmed its protective role as an antioxidant even when it is given in lower doses. The results of the present study were in agreement with the results of \u003cstrong\u003eELDesoky\u003c/strong\u003e \u003cstrong\u003eet al.\u003c/strong\u003e (\u003cstrong\u003e2012\u003c/strong\u003e), who reported that Se had a protective effect against the toxicity of malathion MTN in mice.\u003c/p\u003e\n\u003cp\u003eAs a follow-up to our examinations and related statistical analyses, through which we would like to identify the extent to which liver cells are damaged or not affected by MCP pesticide, our results showed that serum levels of albumin and total protein of G2, which was treated with MCP, did not show any significant difference when compared to the control group, as shown in Table\u0026nbsp;1. These results were in agreement with the findings of Mogda et al. (\u003cspan class=\"CitationRef\"\u003e2009\u003c/span\u003e), who studied the effect of MCP in mice, and some other studies, viz., \u003cstrong\u003eAmirali\u003c/strong\u003e \u003cstrong\u003eet al.\u003c/strong\u003e (\u003cstrong\u003e2011\u003c/strong\u003e), EL-Said et al. (\u003cspan class=\"CitationRef\"\u003e1999\u003c/span\u003e), and \u003cstrong\u003eLarsh\u003c/strong\u003e (\u003cstrong\u003e2011)\u003c/strong\u003e, that studied the effect of OP pesticides on experimental animals. Besides those of groups (3), (4), and (5) that were given different doses of Se in addition to MCP, they did not show any significant difference in serum levels of albumin and total protein from those of G1 and G2 groups, which might be due to the fact that the MCP dose was not enough to affect the targeted cells that produced albumin and total protein.\u003c/p\u003e\n\u003cp\u003eTable\u0026nbsp;(1) also showed that either serum levels of total bilirubin or direct bilirubin were affected following treatment with MCP in G (2), as it showed a highly significant increase in total bilirubin or direct bilirubin levels when compared to the control group, with percentage increases of 61% and 173%, respectively. Our results were in agreement with the studies of Kumar et al. (\u003cspan class=\"CitationRef\"\u003e2018\u003c/span\u003e) and Patel et al. (\u003cspan class=\"CitationRef\"\u003e2012\u003c/span\u003e) that reported that MCP had a toxic effect on the liver of male rabbits. The increase in serum levels of total bilirubin or direct bilirubin following treatment with MCP might be attributed to the fact that either the bile ducts of the liver or the bile duct that leads to the duodenum were blocked and/or it might be due to an abnormal (pathological) increase in RBCs, or it might be due to the fact that the hepatocytes failed to perform their functions regarding protein metabolism (\u003cstrong\u003eChatterjea and Shinde,2005 ; Guyton and Hall,2006\u003c/strong\u003e). With regard to the animals of groups 3, 4, and 5, they were treated with MCP and three different doses of Se. The mean serum levels of T.B and D.B of each group showed non-significant difference when compared to the control group and a significant decrease which was dose dependent with a percentage decrease of 14%, 32%,34% respectively for T.B serum levels and 52%, 54%, 57% respectively for D.B serum levels when compared to MCP group (G2) which might be attributed to the antioxidant effect of Se in G1, G2 and G3 against the induced toxic effect of MCP in such groups which was dose dependent as the dose of Se increased the antioxidant effect against MCP toxicity decreased which agreed with finding of \u003cstrong\u003eALDesoky\u003c/strong\u003e \u003cstrong\u003eet al.\u003c/strong\u003e,(\u003cstrong\u003e2012\u003c/strong\u003e) who reported that Se had a protective role against the toxic effect of malathion pesticides on the liver cells of rats. Hence, we conclude from this study that Se had a protective effect against the hepatotoxicity of MCP pesticide in rabbits.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study confirms that Se completely counteracts MCP-induced hepatotoxicity in male rabbits in a dose-dependent fashion. MCP exposure elevated the activities of liver enzymes (GPT, GOT) and bilirubin, indicating severe hepatic injury. Se supplementation, however, effectively reduced these toxic impacts, with the highest dose (8 µg/kg b.wt) providing the highest protection. The findings suggest Se antioxidant and hepatoprotective activity against organophosphate pesticide toxicity. Further studies need to be conducted to further characterize its molecular mechanisms and therapeutic applications. This study emphasizes the importance of dietary antioxidants as preventive measures against pesticide-induced health risks and the need for greater regulation of pesticides.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eAlb\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlbumin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eALT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlanine Aminotransferase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eAST\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAspartate Aminotransferase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCAT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCatalase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCPAE\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCellular Protective Antioxidant Enzymes\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eD.B\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDirect Bilirubin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eGOT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlutamate Oxaloacetate Transaminase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eGPT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlutamate Pyruvate Transaminase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eGPX\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlutathio Peroxidase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eGSH\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlutathion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eH\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e\u003cb\u003eO\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHydrogen Peroxide\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eLDH\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLactate Dehydrogenase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eLPO\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLipid Peroxidation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eMCP\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMonochrotophos\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eMTN\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMalathion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNS\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNon-Significant\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNO\u003c/b\u003e\u003csub\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sub\u003e\u003csup\u003e\u003cb\u003e\u0026minus;\u003c/b\u003e\u003c/sup\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNitrit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eNO\u003c/b\u003e\u003csub\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sub\u003e\u003csup\u003e\u003cb\u003e\u0026minus;\u003c/b\u003e\u003c/sup\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNitrate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eOps\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOrganophosphates\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eROS\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eReactive Oxygen Species\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eSe\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSelenium\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eSOD\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSuperoxide Dismutase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eT.B\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTotal Bilirubin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eT.P\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTotal Protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e: The experimental procedures involved in the animal-subject experiments were undertaken as per ethical regulations regarding the care and use of laboratory animals. Approval to carry out the study was obtained from the concerned institutional ethics committee, thereby confirming adherence to all relevant animal welfare acts. Every attempt was made to reduce the discomfort of animals, and the fewest number of animals necessary were used to achieve valid scientific data. Approval to participate in this study was gained by following the ethical stipulations and protocols prescribed by the institution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthorization for Dissemination\u003c/strong\u003e: Authors involved in this research provide consent for publication of the research work in an academic journal. They confirm that all the co-authors have read the manuscript and agree to the data and the conclusions drawn. There are no interests which will compromise the integrity of the study, and all the required approvals have been taken for including the material from third party in the publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and information are available\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e The data sets and data considered during the current study are available from the corresponding author upon reasonable request. All data that are important to support the findings of the present study are included in the manuscript. Any supplementary information or materials can be made available when required for future studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicting Interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests in this study. There are no financial, personal, or professional relationships that would affect the research or conclusions of the study..\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNo specific funding was obtained for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' Contributions: FAMQ\u003c/strong\u003e: Conceptualization, methodology, investigation, data collection, analysis and writing of the original draft.\u0026nbsp;\u003cstrong\u003eEMAS\u003c/strong\u003e: Oversight, review, and editing of the manuscript. \u003cstrong\u003eSMK\u003c/strong\u003e: Data curation and formal analysis. \u003cstrong\u003eNMA\u003c/strong\u003e: Manuscript revision, validation, and visualization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003eThe authors would like to offer their sincere thanks to the research team for their commitment and cooperation during the course of this research. We also want to thank Springer Nature and The Journal of Basic and Applied Zoology for their assistance during the publication process. The work contributed by these organizations has been instrumental in making this research successful.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cstrong\u003eAbdulaziz M. Al-Othman, Khaled S. Al-Numair,Gaber E. El-Desoky, Kareem Yusuf, Zaid A. al-Othman, Murad A.M. Aboul\u0026ndash;Soud, and John P.Giesy.(2011).\u003c/strong\u003e Protective of \u0026alpha;-tocopherol and selenium against acute effects of Malathion on liver and kidney of rats .\u003cem\u003eAfr. J. pharmacol,5(8):1054-1062.\u003c/em\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eAboul-soud Mourad A.M , Abdulaziz M Al-Othman , Gaber E El_Desoky, Zaid A Al-othman, Kareem yusuf, Javed Ahmed and Abdulaziz A. Al-Khedhairy.(2011)\u003c/strong\u003e. 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Hum Exp Toxicol.Jul;23(7):323-9. doi: 10.1191/0960327104ht456oa. PMID: 15311849.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"Monochrotophos, Selenium, Antioxidant, Hepatotoxicity","lastPublishedDoi":"10.21203/rs.3.rs-6710706/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6710706/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Monochrotophos (MCP), a widely utilized organophosphate pesticide in agriculture, is highly risky to the hepatic health of most animal species. The present study was designed to examine the hepatotoxicity of MCP on hepatic cells and the probable protective role of Selenium (Se) in male rabbits.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e 25 normal male rabbits, weighing between 1200 and 1500 g, were randomly assigned to five groups. Group 1 served as the control, and Groups 2 to 5 received 0.1 mg/kg of MCP daily for 25 days, with Groups 3, 4, and 5 receiving 2, 4, and 8 µg/kg.b.wt of Se, respectively, in addition. The blood samples collected after treatment were analyzed for serum estimation of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), total protein (T.P), albumin (Alb), total bilirubin (T.B), and direct bilirubin (D.B). Results in this study indicated that MCP exposure considerably increased serum GPT and GOT and T.B. and D.B. levels and decreased the levels of T.P. in comparison to the control group. Conversely, results in Groups 3-5, which were treated with Se, indicated significant improvement in these factors, with levels being almost as high as in the control group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eThe findings suggest that MCP causes severe hepatotoxic effects in male rabbits, while Se plays a protective role against such toxicity. Se supplementation significantly helped in the recovery of serum biomarkers to levels close to normal, thus suggesting its efficacy as an antioxidant in mitigating the liver damage induced by pesticides. The protective effect was found to be directly proportional to the dose given as an index of the importance of dietary antioxidants in reducing the health risks with pesticide exposure. Further research is warranted to explore mechanisms of the Se protective effects and their relevance to human health.\u003c/p\u003e","manuscriptTitle":"Selenium as a Hepatoprotective Agent for Organophosphate Pesticide (Monocrotophos) Toxicity in Male Rabbits","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-05 17:18:43","doi":"10.21203/rs.3.rs-6710706/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":"7c14a09e-3a61-453d-9b38-7c43c0e8e043","owner":[],"postedDate":"June 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-30T12:23:33+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-05 17:18:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6710706","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6710706","identity":"rs-6710706","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}