Metformin attenuates paracetamol-induced hepatorenal damage and oxidative stress in rats

Abstract

Purpose: To evaluate the protective effect of metformin against hepatorenal damage induced by acute paracetamol toxicity in rats. Methods: Twenty Wistar rats of both sexes were divided into four groups (n = 5 each). Groups 1 and 2 received distilled water orally, while groups 3 and 4 received metformin (500 mg/kg) and silymarin (100 mg/kg), respectively, orally once daily for six days. On day 7, paracetamol (3 g/kg) was administered orally to groups 2-4 to induce toxicity. After 24 h, blood samples were collected for the biochemical assessment of liver enzymes (alanine transaminase - ALT, aspartate transaminase - AST, alkaline phosphatase - ALP, and lactate dehydrogenase - LDH), kidney markers (urea and creatinine), and oxidative stress parameters (superoxide dismutase - SOD, catalase - CAT, glutathione - GSH, glutathione peroxidase - GPx, malondialdehyde - MDA, and nitrite). Data were analyzed using one-way ANOVA followed by Tukey's post-hoc test. Results: Paracetamol administration significantly (p < 0.05) elevated liver enzymes, total bilirubin, urea, creatinine, MDA, and nitrite concentrations, while significantly (p < 0.05) reducing antioxidant enzymes and albumin as seen in group 2 compared to group 1. Pretreatment with metformin markedly (p < 0.05) attenuated these alterations, restored liver and kidney biomarkers, and improved antioxidant status. These effects were comparable to those of the silymarin treatment group. Conclusion: Metformin demonstrates significant protective effects against paracetamol-induced hepatorenal toxicity, likely through antioxidant enhancement and reduction of oxidative stress, thus supporting its potential for repurposing to mitigate drug-induced organ injury.