THE PROTECTIVE ROLE OF THYMOL AGAINST METHOMYL- INDUCED TOXICITY IN MALE RATS: CLINICO-BIOCHEMICAL, HISTOPATHOLOGICAL AND IMMUNO-HISTOCHEMICAL STUDIES
DOI:
https://doi.org/10.26873/SVR-1441-2021Keywords:
Methomyl, Thymol, oxidative stress, caspase 3, rats, spermAbstract
This experiment was carried out to evaluate the presumptive protective effect of thymol (T) against methomyl (M) - induced toxicity in male albino rats. Therefore, forty adult healthy male albino rats were randomly divided into 4 equal groups as follow: control group, intoxicated group received methomyl (4 mg/kg b.wt./day), treated group received thymol (100 mg/kg b.wt.), and co-treated group received both methomyl and thymol with the previous doses. The treatment regimens were given orally three times a week, day after day, for eight weeks. Biochemically, the M- intoxicated rats revealed a significant increase in the serum aminotransferases (ALT& AST) and gamma glutamyle transferase (GGT) activities, total, direct and indirect bilirubin, total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C), urea, malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity, in addition to a significant decrease in serum albumin and testosterone levels with a significant increase in the percentage of sperm abnormalities in comparison with the control rats. Regarding to the histopathological examination, M- intoxicated group showed degenerative and necrotic lesions in the hepatic, renal and testicular tissues. But, the co- treatment with thymol ameliorated the M- induced biochemical alterations, oxidative stress and apoptosis and improved tissues architecture. It could be concluded that co-treatment with thymol may provide a prolonged remedy against methomyl -induced toxicity.
References
● 1. Pushpalatha M, Balaji K, Kumar PC, Sridevi C, Reddy CS. Study of the electrochemical behaviour and analysis of methomyl in environ-mental samples. Asian J Biochem Pharm Res 2013; 3: 64–73.
● 2. Shalaby MA, El Zorba HY, Ziada RM. Reproductive toxicity of methomyl insecticide in male rats and protective effect of folic acid. Food Chem Toxicol 2010; 48: 3221–6.
● 3. WHO (World Health Organiza-tion). International Program on chemical safety: Collaborative pro-gram of the United Nations Envi-ronment Program, the International Labour Organization. Geneva. 1995; EB95/29:1-9. https://www.google.com/url?q=ht tp s://apps.who.int/iris/bitstream/handle/10665/172 136/EB95_29_eng.pdf%3Fsequence%3D1%26isAllowed%3Dy&sa=U&ved=2ahUKEwi5j7H-45DzAh VM5uAKHSfOA8wQFnoECAUQAg&usg=AOvVaw1kyvA700sTRJ2ga3co2MOj
● 4. El-Khawaga OY. Protective effects of tannic acid against methomyl-induced-oxidative stress. J Bio-technol Biomaterial 2012; 2: 127-30.
● 5. Van Scoy AR, Yue M, Deng X, Tjeerdema RS. Environmental fate and toxicology of methomyl. Rev Environ Contam Toxicol 2013; 222: 93–109.
● 6. Djeffal A, Messarah M, Bou-mendjel A, Kadeche L, Feki AE. Protective effects of vitamin C and selenium supplementation on methomyl induced tissue oxidative stress in adult rats. Toxicol Ind Health 2015; 31:31–43.
● 7. Andersen HR, Vinggaard AM, Rasmussen TH, Gjermandsen IM, Bonefeld-Jørgensen EC. Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activity in vitro. Toxicol Appl Pharmacol 2002; 179: 1–12.
● 8. Mansour SA, Abbassy MA, Shal-dam HA. Zinc ameliorate oxidative stress and hormonal disturbance induced by methomyl, abamectin, and their mixture in male rats. Tox-ics 2017; 5: 37–53.
● 9. Yu YM, Chao TY, Chang WC, Chang MG, Lee MF. Thymol re-duces oxidative stress, aortic intimal thickening, and inflammation-related gene expression in hyper-lipidemic rabbits. J Food Drug Anal 2016; 24: 556–63.
● 10. Liang D, Li F, Fu Y, et al. Thymol inhib-its LPS stimulated inflammatory response via down-regulation of NF-κB and MAPK signaling pathways in mouse mammary epithelial cells. Inflammation 2014; 37: 214–22.
● 11. Meeran MF. Prince PS. Protective effects of thymol on altered plasma lipid peroxidation and nonenzymat-ic antioxidants in isoproterenol-induced myocardial infarcted rats. J Biochem Mol Toxicol 2012; 26:368–73.
● 12. Garg DP, Bansal AK, Malhotra A, Kiran R, Dhawan DK. Methomyl induced hematological and bio-chemical alterations – protection by vitamin E. Pestic Biochem Physiol 2009; 93: 127–32.
● 13. Tahmasebi P, Froushani SM, Ahangaran NA. Thymol has beneficial effects on the experimental model of ulcerative colitis. Avicenna J Phytomed 2019; 9: 538–50.
● 14. Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957; 28: 56–63.
● 15. Szasz G. A Kinetic photometric method for serum γ-Glutamyl transpeptidase. Clin Chem 1969; 15: 124–36.
● 16. Doumas BT, Bayse DD, Carter RJ, Peters TJ, Schaffer R. A candi-date reference method for deter-mination of total protein in serum. I. Development and validation. Clin Chem 1981; 27:1642–50.
● 17. Doumas BT, Watson WA, Biggs HG. Albumin standards and the measurement of serum albumin with bromcresol green. Clin Chim Acta 1971; 31: 87–96.
● 18. Walter MI, Gerade HW. An ul-tramicromethod for the determina-tion of conjugated and total biliru-bin in serum or plasma. Micro Chem J 1970; 15: 231–43.
● 19. Allain C, Poon L, Chan C, Rich-mond W, Fu P. Enzymatic deter-mination of total serum cholesterol. Clin Chem 1974; 20: 470–75.
● 20. Fassati P, Prencipe L. Serum tri-glycerides determined colorimetri-cally with an enzyme that produces hydrogen peroxide. Clin Chem 1982; 28: 2077–80.
● 21. Lopez – Virella M, Stone S, Ellis J. A. and Colwell J. Cholesterol de-termination in high-density lipopro-teins separated by three different methods. Clin Chem 1977; 23: 882–4.
● 22. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipo-protein cholesterol in plasma, with-out use of the preparative ultracen-trifuge. Clin Chem 1972; 18: 499–2.
● 23. Rock R, Walker W, Jennings C. Nitrogen metabolites and renal function. In: Tietz N, ed. Funda-mentals of clinical chemistry. 3rd ed. Philadellphia: Saunders W, 1987: 669–704.
● 24. Fabiny D, Ertingshausen G. Au-tomated reaction-rate method for determination of serum creatinine with the CentrifiChem. Clin Chem 1971; 17: 696–700.
● 25. Ohkawa H, Ohishi W, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reac-tion. Anal Biochem 1979; 95: 351–8.
● 26. Sedlak J, Lindsay R. Estimation of total protein-bound and non-protein sulfhydryl groups in tissue with Ellman’s reagent. Anal Bio-chem 1968; 25: 192–205.
● 27. Nishikimi M, Appaji N, Yagi K. The occurrence of superoxide ani-on in the reaction of reduced phen-azine methosulfate and molecular oxygen. Biochem Biophys Res Commun 1972; 46: 849–54.
● 28. Tietz N. Clinical Guide to Labora-tory Tests (ELISA). 3rd ed, Saun-ders W, Co. Philadelphia, 1995: 22–3.
● 29. Bearden HJ, Fuquay JW. Semen evaluation. In: Bearden HJ, Fuquay JW, eds. Applied animal reproduc-tion. New Jersey7 Prentice Hall, 2000: 168–82.
● 30. Bancroft J, Gamble M. Theory and practice of histological tech-niques. 6th ed, Churchill Living-stone, Elsevier, London, 2008: 105–34.
● 31. Ramos-Vara J. Technical aspects of immunohistochemistry. Vet Pathol 2005; 42: 405–26.
● 32. SAS (Statistical Analysis System). Version 9.30, User’s Guide. SAS Institute Inc., Cary, NC, USA, 2011.
● 33. Weng J, Cai B, Chen J, et al. Met-abolic changes in methomyl poi-soned rats treated by vitamin E. Hum Exp Toxicol 2018; 37: 390–8.
● 34. Cano-Europa E, Blas-Valdivia V, Franco- Colin M, Gallardo-Casas CA, Ortiz-Butron R. Methimazole-induced hypothyroidism causes cel-lular damage in the spleen, heart, liver, lung and kidney. Acta Histo-chem 2011; 113:1–5.
● 35. Patil JA, Patil AJ, Govindwar SP, Sontakke AV. Protection of liver in-jury by vitamin C, E and GSH after methomyl toxicity in rat. J Pharm Chem Biol Sci 2016; 3: 506–17.
● 36. Mansour SA, Ali AR, Mohamd RI. Ameliorating effect of green tea, sage, and their mixture against methomyl-induced physiological, biochemical and histopathological alterations in male rats. Egypt Pharmaceut J 2018; 17: 223–36.
● 37. Chabane K, Khene MA, Zaida F, et al. Subacute and subchronic methomyl exposure induced toxic effects on intestines via oxidative stress in male albino rats: biochem-ical and histopathological study. Drug Chem Toxicol 2020; 32: 1–14.
● 38. Rašković A, Pavlović N, Kvrgić M et al. Effects of pharmaceutical formulations containing thyme on carbon tetrachloride- induced liver injury in rats. BMC Complementary Alternat Med 2015; 15:1–11.
● 39. Nyblom H, Berggren U, Balldin J, Olsson R. High AST/ALT ratio may indicate advanced alcoholic liver disease rather than heavy drinking. Alcohol Alcohol 2004; 39: 336–9.
● 40. Abdel Aziz II, Zabut BM. Altera-tions of blood indices associated with low-dose administration of methomyl insecticide for short times to albino rats. Egypt J Biol 2014; 16: 17–23.
● 41. Mokhtar HI, Abdel-Latif HA, ElMazoudy RH, Abdelwahab WM, Saad MI. Effect of methomyl on fertility, embryotoxicity and physio-logical parameters in female rats. J Appl Pharm Sci 2013; 3:109–19.
● 42. Hashish E, Elgaml SA. Role of nicotinic acid in mitigating metho-myl induced acute toxicity in albino rats. J Clin Exp Pathol 2016; 6: 268.
● 43. Galli GM, Gerbet RR, Griss LG, et al. Combination of herbal com-ponents (curcumin, carvacrol, thy-mol, cinnamaldehyde) in broiler chicken feed: Impacts on response parameters, performance, fatty acid profiles, meat quality and control of coccidia and bacteria. Microb Pathog 2020; 139: 103916–49.
● 44. Elshopakey GE, Risha EF, El-Boshy ME, Abdalla OA, Hamed MF. Protective effects of thymus vulgaris oil against ccl4- mediated hepatotoxicity, oxidative stress and immunosuppression in male albino rats. Adv Anim Vet Sci 2021; 9: 1053–63.
● 45. El-Boshy M, Refaat B, Qasem A, et al. The remedial effect of Thymus vulgaris extract against lead toxicity-induced oxidative stress, hepato-renal damage, immunosuppression and hematological disorders in rats. Environ Sci Pollut Res 2019; 26: 1–11.
● 46. Ibrahim NA, El-Gamal BA. Ef-fect of diazinon, an organophos-phate insecticide on plasma lipid constituents in experimental ani-mals. J Biochem Mol Biol 2003; 36: 499–504.
● 47. Mansour SA, Mossa AH, Heikal TM. Effects of methomyl on lipid peroxidation and antioxidant en-zymes in rat erythrocytes: in vitro studies. Toxicol Ind Health 2009; 25: 557–63.
● 48. Glaser G, Mager J. Biochemical studies on the mechanism of liver poisons. II. Induction of fatty liver. Biochim Biophys Acta 1972; 261: 500–7.
● 49. Abdel-Wareth AA, Al-Kahtani MA, Alsyaad KM, et al. Combined supplementation of nano-zinc oxide and thyme oil improves the nutrient digestibility and reproductive fertili-ty in the male californian rabbits. Animals 2020; 1: 2234.
● 50. Kokhdan EP, Sadeghi HS, Kazemi S, Doustimotlagh AH. Nephroprotective effects of Zataria multiflora boiss. hydroalcoholic ex-tract, carvacrol, and thymol on kid-ney toxicity induced by cisplatin in rats. Evid Based Complementary Altern Med 2021; ID 8847212:1–7.
● 51. Sakr S, Hassanien H, Bester MJ, et al. Beneficial effects of folic acid on the kidneys and testes of adult albino rats after exposure to methomyl. Toxicol Res 2018; 7: 480–91.
● 52. Abdelkhalek MR, El-Khawaga OY, Elbnhawy RA, El-Gayar HA. Green tea attenuates methomyl-induced cardiac toxicity through modulating oxidative stress and nu-clear factor kappa B Up- regulation in mice. Egypt J Basic Appl Sci 2021; 8: 136–45.
● 53. Coursin DB, Chilla HP, Will JA, Mccreary JL. Adaptation to chronic hyperaxia. Biochemical effects and the response to subsequent lethal hyperoxia. Am Rev Respir Dis 1985; 135: 1002–6.
● 54. Moeen D, Amer A, Ismail N, Ali E. Possible action of grape seed oil on brain toxicity induced by methomyl or imidacloprid of male rats. J Sci Res Sci 2018; 35: 250–72.
● 55. Mahgoub AA, El-Medany AH. Evalua-tion of chronic exposure of the male rat reproductive system to the insecticide methomyl. Pharmacol Res 2001; 44: 73–80.
● 56. Yousef MI, El-Demerdash FM, Kamil KI, Elaswad FA. Ameliorat-ing effect of folic acid on chromi-um (VI)-induced changes in repro-ductive performance and seminal plasma biochemistry in male rab-bits. Reprod Toxicol 2006; 2: 322-28.
● 57. El-Gindy YM. Improvement in quality and storage ability of rabbit semen by using black or thyme seed as dietary supplementation. J Anim Physiol Anim Nutr 2021; 00: 1-13.
● 58. Meng SL, Liu T, Chen X, et al. Effect of chronic exposure to methomyl on tissue damage and apoptosis in testis of tilapia (Oreo-chromis niloticus) and recovery pat-tern. Bull Environ Contam Toxicol 2019; 102: 371-76.
● 59. Jafari A, Karimipour M, Khaksar M, Ghasemnejad-Berenji M. Pro-tective effects of orally adminis-tered thymol against titanium diox-ide nanoparticle–induced testicular damage. Environ Sci Pollut Res Int 2020; 27: 2353-60.
● 60. Mazen NF, Elnegris HM. Role of coenzyme Q10 in testicular damage induced by acrylamide in weaned albino rats: a histological and im-munohistochemical study. Egypt J Histol 2013; 36: 164-74.
● 61. Aboul-Soud MA, Al-Othman AM, El-Desoky GE, et al. Hepatopro-tective effects of vitamin E/selenium against malathion-induced injuries on the antioxidant status and apoptosis-related gene expression in rats. J Toxicol Sci 2011; 36: 285 – 96.
● 62. Mahdi H, Tahereh H, Esmaiel S, Massood E. Vitamins E and C pre-vent apoptosis of testicular and ovarian tissues following mancozeb exposure in the first-generation mouse pups. Toxicol Ind Health 2019; 35: 136-44.
● 63. Heikal TM, Mossa AH, Khalil WK. Protective effects of vitamin C against methomyl-induced injures on the testicular antioxidant status and apoptosis-related gene expres-sion in rat. J Environ Anal Toxicol 2014; 4: 255.
● 64. Aksu EH, Kandemir FM, Altun S, Küçükler S, Çomaklı S, Ömür AD. Ameliorative effect of carvacrol on cisplastin‐induced reproductive damage in male rats. J Biochem Mol Toxic 2016; 30: 513-20.
● 65. Karimi S, Hosseinimehr SJ, Mo-hammadi HR, Khalatbary AR, Amiri FT. Zataria multiflora amelio-rates cisplastin-induced testicular damage via suppression of oxidative stress and apoptosis in a mice model. Iran J Basic Med Sci 2018; 21:607-14.
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