Comparing the protective effects of L-carnitine and Silybum marianum aqueous extract after diazinon-induced hepatotoxicity in male rat liver

Document Type : Research Articles


Department of Biology, Kazerun Branch, Islamic Azad University, Kazerun, Iran


Diazinon (DZN), as an organophosphorus pesticide (OP), induces oxidative stress leading to the generation of free radicals and causes some pathological changes in the body. The purpose of this study was to assess the protective effects of L-carnitine (LC) and Silybum marianum aqueous extract (SMAE) against DZN-induced hepatotoxicity in male rat liver. Rats were assigned in 9 groups (n=8) including control, sham, DZN15, SMAE100, LC300, SMAE100+LC300, DZN15+LC300, DZN15+SMAE100 and DZN15+SMAE100+LC300. Thirty days after the treatment by oral gavage, blood samples were taken and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), Albumin (Alb) and total protein (TP) were measured using photometric method. Besides, the livers of rats were removed and evaluated histopathologically. The DZN15 treatment significantly increased the AST, ALT, ALP and GGT levels (p<0.05) and conversely decreased the Alb and TP levels (p<0.05). Moreover, administration of the DZN15 resulted in lymphocytic inflammation, congestion, apoptosis hepatocyte, and lesser sinusoids space. However, the DZN15+SMAE100+LC300 treatment did not change the ALT, ALP, GGT, Alb and TP levels (p˃0.05) but increased the AST level significantly compared to the control (p<0.05). Besides that, lesser structural alterations and improvement in the liver tissue were observed. The findings suggest that co-administration of SMAE and LC could reduce DZN-induced hepatic tissue damages and improve the hepatic biochemical parameters in rats.


Main Subjects

1. Raju SBG, Battu RG, Manju latha YB, Srinivas K. Antihepatotoxic activity of smilax china roots on CCL4 induced hepatic damage in rats. Int J Pharm Pharm Sci. 2012;4:494-6.
2. Pehkonen SO, Zhang Q. The degradation of organophosphorus pesticides in natural waters: A critical review. Crit Rev Env Sci Tec. 2002;32:17-72.
3. GarWtt SJ, Jones K, Mason HJ, Cocker J. Exposure to the organophosphate diazinon: data from a human volunteer study with oral and dermal doses. Toxicol Lett. 2002;134:105-13.
4. Ogutcu A, Uzunhisarcikli M, Kalender S, Durak D, Bayrakdar F, Kalender Y. The effects of organophosphate insecticide diazinon on malondialdehyde levels and myocardial cells in rat heart tissue and protective role of vitamin E. Pes Biochem Physiol. 2006;86:93-98.
5. Abdollahi M, Mostafalou S, Pournourmohammadi S, Shadnia S. Oxidative stress and cholinesterase inhibition in salvia and plasma of rats following subchronic exposure to malathion. Comp Biochem. Physiol. 2004;137:29-34.
6. Singh B, Dogra TD, Tripathi CB. A study of serum cholinesterase activity in agricultural and industrial workers occupationally exposed to organophosphates insecticides. Int J Med Toxicol. 2002;5:2-5.
7. Zhang HX, Sultatos LG. Biotransformation of the organophosphorus insecticides parathion and methyl effects of black tea extract. Clinica Chimica Acta. 2005;358:131-38.
8. Kappers WA, Edwards RJ, Murray S, Boobis AR. Diazinon is activated by CYP2C19 in human liver. Toxicol Appl Pharmacol. 2001;177:68-76.
9. Mohamed SS, Desouky TA, Mohamed SR, Naguib KM, Helmy MH. Antioxidant compounds from rice straw extract and their effect on diazinon insecticide hazard. Middle East J Appl Sci. 2015;5:687-94.
10. Sargazi Z, Nikravesh MR, Jalali M, Sadeghnia HR, Rahimi Anbarkeh F. Apoptotic effect of organophosphorus insecticide diazinon on rat ovary and protective effect of vitamin E. IJT. 2016;10:37-44.
11. Tsitsimpikou C, Tzatzarakis M, Fragkiadaki P, Kovatsi L, Stivaktakis P, Kalogeraki A, et al. Histopathological lesions, oxidative stress and genotoxic effects in liver and kidneys following long term exposure of rabbits to diazinon and propoxur. Toxicology. 2012; 307: 109-14.
12. Kolodziejczyk J, Saluk-JuszczakJ, Wachowicz B. L-carnitine protects plasma componentsagainst oxidative alterations. Nutrition. 2011;27:693-99.
13. Ribas G, Manfredini V, Marco M, VieiraR, WayhsC, Vanzin C, et al. Prevention by l-carnitine of DNA damage induced by propionic and l-methylmalonic acids in human peripheral leukocytes in vitro. Mutat Res. 2010;702:123-28.
14. ArokiaRani P, Panneerselvam C. Carnitine as a free radical scavenger an aging. Exp Gerontol. 2001;36:1713-26.
15. SteiberA, Kerner J, Hoppel C. Carnitine: a nutritional, biosynthetic and functional perspective. Mol Aspects Med. 2004;25:455-73.
16. Sayed-Ahmed M. Role of carnitine in cancer chemotherapy-induced multiple organ toxicity. Saudi Pharm J. 2010;18:195-206.
17. Francis R. The wild flower hey. 4th ed. Frederick: Warne Publisher; 2006.
18. Cacho M, Moran M, Corchete P, Fernandez Tarrago J. Influence of medium composition on the accumulation of flavonolignans in cultured cells of Silybum marianum (L.) Gaertn. Plant Sci. 1999;144:63-68.
19. Kumar Kalla P, Chitti S, Aghamirzaei ST, Senthilkumar R, Arjunan S. Anti-cancer activity of silymarin on MCF-7 and NCIH-23 cell lines. Adv Biol Res. 2014;8:57-61.
20. Gupta OP, Sing S, Bani S, Sharma N, Malhotra S, Gupta BD, et al. Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase. Phytomedicine. 2000;7:21-24.
21. Gomes J, Dawodu AH, Lloyd O, Revitt DM, Anilal SV. Hepatic injury and disturbed amino acid metabolism in mice following prolonged exposure to organophosphorus pesticides. Hum Exp Toxicol. 1999;18:33-37.
22. Solati A. Tavasoli A. Koohi MK, Marjanmehr SH, Nekouie Jahromi OA. The toxico pathologic effects of Diazinon on histopathological biochemical and hemathological parameters in Rabbits by dermal exposure of toxin. J Vet Res. 2011;66:103-12.
23. Gockcimen A, Gulle k, Demirin H, Bayram D, Kocak A, Altunsa I. Effects of diazinon atdifferent doses on rat liver and pancreas tissues. Pest Bp. 2007;87:103-108.
24. Altuntas I, Kilinc I, Orhan H, Demirel R, Koylu H, Delibas N. The effects of diazinon on lipid peroxidation and antioxidant enzymes in erythrocytes in vitro. Hum Exp Toxicol. 2004; 23:9-13.
25. Fattahi, E, Parivar K, Jorsaraei SGA, Moghadamnia AA. The effect of diazinon on the leydig cells and the level of sex hormones in mice. J Babol Univ Med Sci. 2007;9:15-22.
26. Osawa T, Kato Y. Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia. Ann NY Acad Sci. 2005;1043:440-51.
27. Schuppan D, Jia JD, Brinkhaus B, Hahn EG. Herbal products for liver diseases. Hepatology 1999;30:1099-1104.
28. Campos R, Garrido A. Silybin dihemsuccinate protects against glutathioine depletion and lipid peroxidation induced by acetaminophen on rat liver. Plant. Meidca. 1998; 55:417-429.
29. Gazak R, Wahterova D and Kren V. Silybin and Silymarin. New and emerging applications in medicine. Current Medicinal Chemistry 2007;14:1-23.
30. El-habit O, Ahmed M, Gabry M, Kahil M, Osman A. Modulation of induced cardiocytotoxiciry and genotoxicity of Doxorubicin in rat by L-Carnitine. J egy Nat Cancer Inst 2000;12:267-274.
31. Karlic H, Lohninger A. Supplementation of L-carnitine in athletes: does it make sense? Nutrition 2004;20:709-15.
32. Peyrat-Maillard MN, Bonnely S, Berset C. Determination of the antioxidant activity of phenolic compounds by coulometric detection. Talanta. 2000;51:709-16.
33. Zix MH, Agarwal R. Novel cancer chemopreventive effects of a flavonoid antioxidant silymarin. Biochm Biophys Res Commun. 1997;239:334-39.
34. Schonfeld JV, Weisbrod B, Muller MK. Silibinin aplant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporine toxicity. CMLS. 1997;53:917-20.
35. Gulcin I. Antioxidant and antiradical activities of L-carnitine. Life Sci. 2006;78:803-11.
36. Rezaei-Tavirani M, Mahdavi SM, Hei darian E. Electrochemical study of attaching the active substance HPB to human serum Albumin. J Ilam Uni Med Sci. 2006;4:38-43.
37. Yehia M, El-Banna SG, Okabm AB. Diazinon toxicity affects histophysiological and biochemical parameters in rabbits. Exp Toxicol Pathol. 2006;59:215-25.
38. Sajadi SM, Nasrollahzadeh M, Maham M. Aqueous extract from seeds of Silybum marianum L. as a green material for preparation of the Cu/Fe3O4 nanoparticles: A magnetically recoverable and reusable catalyst for the reduction of nitroarenes. J Colloid Interface Sci. 2016;469:93-98.
39. Woodward K, Marrs T, Waters MD. Toxicological effects of veterinary medicinal products in humans. 1th ed. Cambridge: RSCPress; 2012.
40. Rahimi. S. Zamiri MJ. Shariati M. Changizi-Ashtiyani S. Moghadamnia D. Rahimi A. Effect of Diazinon on pituitary-gonadal axis and histological alteration of seminiferous tubules in adult rat testis. J Gorgan Univ Med Sci. 2016;18:23-28.
41. Hussein SA, Abd El-Hamid OM, Hemdan HS. Protective effect of l-carnitine on metabolic disorders, oxidative stress, antioxidant status and inflammation in a rat model of insulin resistance. BVMJ. 2013; 25:99-112.