Protective effects of metformin against doxorubicin-induced hepatoxicity in rats

Abstract Purpose Doxorubicin (DOX) is one of the most commonly prescribed anti-cancer drugs. However, DOX-induced hepatotoxicity is a dose-limiting side effect. This study aimed to clarify the potential protective effects of metformin on DOX-induced hepatotoxicity in rats. Methods The animals were divided into six groups (n=6 each): Control Group, DOX group, metformin 200 mg/kg group, DOX + metformin 50 mg/kg group, DOX + metformin 100 mg/kg group, and DOX + metformin 200 mg/kg group. Hepatic injury was induced by a single intraperitoneal injection of DOX (20mg/kg). The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in serum were determined. Furthermore, the hepatic histopathological changes were evaluated. In order to identify the markers of oxidative stress, the level of malondialdehyde (MDA) and the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in liver tissue were measured. Results Results showed that DOX provoked a marked elevation in ALT, AST, and ALP serum levels. In addition, oxidative stress was significantly boosted in DOX-treated rats compared to control rats. All these were abolished with the metformin administration. Histological examination also showed that metformin could significantly reduce DOX-induced alterations. The most prominent effect was observed by high-dose metformin. Conclusion This study showed that metformin could prevent doxorubicin-induced hepatoxicity.