Hepatoprotective effect of DL-methionine on diclofenac-induced hepatotoxicity in albino rats: an experimental study
Keywords:Diclofenac, Drug-induced hepatotoxicity, Liver injury, NSAIDs, Serum markers
Background: Liver is the main detoxifying organ, which is affected by most of the drugs and xenobiotic agents that could result in liver damage. The present study was designed to evaluate the hepatoprotective effect of DL-Methionine against experimentally induced liver injury in albino rats.
Methods: Hepatotoxicity was induced by administering high doses of positive control drug Diclofenac sodium in albino rats, which was confirmed by estimating Liver Function Tests. Hepatoprotective effect was determined by administering DL- Methionine concomitantly with positive control drug. Albino rats were administered with DL-Methionine (700 mg/kg and 1400 mg/kg) respectively as a single oral dose, concomitantly with positive control drug Diclofenac sodium (96 mg/kg and 240 mg/kg) respectively. After 24-hours of post-treatment, serum levels of the liver enzymes were evaluated to demonstrate the hepatoprotective effect of DL-Methionine on drug-induced hepatotoxicity, and all the liver samples were examined for the histopathological study.
Results: Significant increase in serum transaminase enzymes were observed by the positive control drug Diclofenac sodium. There was significant reduction in the serum transaminases on concomitant administration of DL-Methionine with Diclofenac sodium. Liver injury induced by positive control drug; and its protection with DL-Methionine was revealed by histopathological study. The combination of Diclofenac sodium and DL-Methionine showed no significant histopathological difference when compared to the normal liver section.
Conclusions: The results reveal that, DL-Methionine significantly prevented the rise in transaminases levels produced by hepatotoxic doses of the positive control drug.
Maity T, Ahmad A. Protective effect of Mikania scandens (L.) Willd. against Isoniazid induced hepatotoxicity in rats. Int J Pharm Pharm Sci. 2012; 4: 466-469
Bell LN, Chalasani N. Epidemiology of idiosyncratic drug-induced liver injury. Semin Liver Dis. 2009 Nov; 29 (4):337-47.
Ervilla Dass E., and Shah K.K., Paracetamol and Conventional anti malarial drugs induced hepatotoxicity and its protection by methionine in rats. Indian J. Exp. Biol. 2000, (38), 1138-1142.
DP Parikh, B. M. Sattigeri, et al. A survey study on use of over the counter (OTC) drugs among medical students, nursing and clerical staff of a tertiary care teaching rural hospital. Int J Res Med Sci. 2013; 1(2), 83-86.
Watkins PB Drug safety sciences and the bottleneck in drug development. Clin Pharmacol Ther. 2011; Jun 89(6):788-90.
Iredale JP, Benyon RC, Pickering J, McCullen M, Northrop M, Pawley S, Hovell C, Arthur MJ. Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J Clin Invest. 1998 Aug 1;102(3):538-49.
Mitchell JR, Jollow DJ, Potter WZ, Gillette JR, Brodie BB. Acetaminophen‐induced hepatic necrosis. IV. Protective role of glutathione. J Pharmacol Exp Ther. 1973 Oct;187(1):211‐217.
Vale JA, Meredith TJ, Goulding R. Treatment of acetaminophen poisoning. The use of
oral methionine. Arch Intern Med. 1981 Feb 23;141(3 Spec No):394‐6.
Piperno E, Berssenbruegge DA. Reversal of experimental paracetamol toxicosis with
N‐acetylcysteine. Lancet. 1976 Oct 2;2(7988):738‐9.
Leiber CS. S-Adenosyl-L-methionine: its role in the treatment of liver disorders. The American Journal of Clinical Nutrition, Volume 76, Issue 5, 1 November 2002, Pages 1183S–1187S,
Mato JM, Lu SC. Role of S-adenosyl-L-methionine in liver health and injury. Hepatology. 2007 May; 45(5):1306-12.
Purohit V, Abdelmalek MF, Barve S, Benevenga NJ, Halsted CH, Kaplowitz N, Kharbanda KK, Liu QY, Lu SC, McClain CJ, Swanson C, Zakhari S. Role of S-adenosylmethionine, folate, and betaine in the treatment of alcoholic liver disease: summary of a symposium. Am J Clin Nutr. 2007 Jul; 86(1):14-24.