Publication:

Assessment of antioxidant activity of metformin in ethanol induced liver damage in Sprague Dawley rats

Background Alcoholic liver disease (ALD) is a life style associated and one of the most common causes of chronic liver disease in the world. Chronic and excessive ethanol consumption impairs fatty acid oxidation and thereby stimulates lipogenesis, which leads to steatosis. Manifestation of harmful effects by alcohol occurs by free radical species which react with most of the cell components by changing their structures and functions. The hepatoprotective activity of metformin may be due to its antioxidant effect and enhancing fatty acid oxidation. So the aim of the present study is to evaluate preventive hepatoprotective effect of metformin in terms of hepatic oxidative stress marker enzymes and liver-histopathology scores.

Methods Thirty adult Sprague Dawley rats of either sex, weighing 200-250 g were selected for the study. The study was performed as per CPCSEA guidelines. The rats were randomly divided into 5 groups; n=6. All the treatments were given once a day for 21 days. After day 21, the dissected liver was used to assess oxidative stress marker enzymes malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) spectrophotometrically. The liver damage was assessed by histopathological scoring (HPS).

Results A comparison of The liver tissue MDA, SOD, CAT levels (nmol/g) and HPS value in the various groups on day-22 suggests that a treatment with metformin at low dose displayed a minimal hepatocellular protection when compared to that of the ethanol-treated and vehicle treated groups; however, metformin treatment at moderate and high doses elicited a better hepato protection as compared to low dose metformin treated groups. A dose-dependent hepatoprotection by metformin that high-dose metformin may be a potential therapeutic candidate in attenuating the ALD.

Conclusions Metformin co-administration effectively prevented hepatic damage caused by ethanol in animal model with favourable modification in the oxidative stress marker enzymes in liver tissue and histopathology. It may be effective for preventing liver toxicity in chronic alcoholics. A dose dependent hepatoprotection reveals that metformin may be a potential therapeutic candidate in attenuating the ALD which needs a systematic clinical study.