Bergenin Attenuates Sodium Selenite-Induced Hepatotoxicity via Improvement of Hepatic Oxidant-Antioxidant Balance in HepG2 Cells and ICR Mice

Abstract

Abstract Bergenin is a C-glucoside derivative of gallic acid claimed to exhibit antioxidant and hepatoprotective activities. However, its effect on sodium selenite-induced oxidative damage has never been elucidated. We investigated the impact of bergenin on the oxidant-antioxidant balance in sodium selenite-induced oxidative stress in HepG2 cells and mouse livers. HepG2 cells were co-incubated with sodium selenite (10 μM) and either bergenin (75, 150, and 300 μM) or gallic acid (60 μM) for 24 h. Adult male ICR mice were orally administered sodium selenite (4 mg/kg/day) in combination with either bergenin (10, 50, and 250 mg/kg/day) or gallic acid (100 mg/kg/day) for 7 days. Sodium selenite injured HepG2 cells and mouse livers by disturbing the oxidant-antioxidant balance. Bergenin exerted protective effects against sodium selenite-induced oxidative stress in HepG2 cells. Moreover, bergenin attenuated sodium selenite-induced liver damage (nuclear pyknosis and necrotic areas) through a decrease in plasma aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels, and decreased production of reactive oxygen species, resulting in reduced lipid peroxidation in plasma and livers. Bergenin also restored hepatic antioxidant enzyme expression levels and activities (superoxide dismutase, catalase, and glutathione peroxidase) and reinstated hepatic glutathione homeostasis. Finally, bergenin returned cytochrome P450 2E1 mRNA expression to normal levels. In conclusion, bergenin reduced-sodium selenite induced liver damage by restoring the oxidant-antioxidant balance and reducing lipid peroxidation through multiple pathways.