Hepatorenal Repercussions of Alcoholic Exposure in a Rat Model: a Dose-Dependent Study of Metformin Intervention

Background: Diabetes mellitus is an alarming life style disease in the modern world. Exploitation of the anti-diabetic drugs for the amelioration of diabetes and associated life style diseases has become an imperative concern. In this milieu, this study was designed to explore the plausible effects of metformin intervention on hepatic and renal functions in a rat model of alcoholic liver disease. Methods: Thirty rats were divided into five groups (n = 6): ethanol control, ethanol water and also low, moderate and high doses of metformin. Ethanol 20% v/v (1 ml/100 g) was administered by oral gavage (p.o.) to all five groups for 21 days. Blood and tissue samples were collected for the assessment of lipid profile, hepatic and renal functions. Results: After 21 days, the levels of hepatic function and lipid parameters were maintained at normalcy, especially in the high-dose metformin treated alcoholic rats as compared to the levels at day 1. Despite this, the renal biomarkers did not display any significant variation due to ethanolic exposure in any group. The histopathological score portrayed that the noxious effect of ethanol is prevented in the liver of moderate- and high-dose metformin, whereas the renal histological scores were unchanged in all the groups including ethanol control. Conclusion: These results suggest that the dose of ethanol required to induce hepatic dysfunction does not influence renal functions. In addition, high-dose metformin offers maximal hepatoprotection and spares kidney from per se toxicity, thereby advocating the beneficial intervention of the anti-diabetic drug, metformin, in alcoholic liver dysfunction.