Involvement of catalase in the protective benefits of metformin in mice with oxidative liver injury

• Metformin alleviated CCl4-induced oxidative injury in liver.
• Metformin enhanced CAT activity but it did not alter the protein level of CAT.
• Metformin activated AMPK but AMPK activator had no obvious effects on CAT.
• Molecular docking analysis indicated that metformin directly contacted with CAT.

Metformin is a commonly used anti-diabetic drug with AMP-activated protein kinase (AMPK)-dependent hypoglycemic activities. Recent studies have revealed its anti-inflammatory and anti-oxidative properties. In the present study, the anti-oxidative potential of metformin and its potential mechanisms were investigated in a mouse model with carbon tetrachloride (CCl4)-induced severe oxidative liver injury. Our results showed that treatment with metformin significantly attenuated CCl4-induced elevation of serum aminotransferases and hepatic histological abnormalities. The alleviated liver injury was associated with decreased hepatic contents of oxidized glutathione (GSSG) and malondialdehyde (MDA). In addition, metformin treatment dose-dependently enhanced the activities of catalase (CAT) and decreased CCl4-induced elevation of hepatic H2O2 levels, but it had no obvious effects on the protein level of CAT. We also found that metformin increased the level of phosphorylated AMP-activated protein kinase (AMPK), but treatment with AMPK activator AICAR had no obvious effects on CAT activity. A molecular docking analysis indicated that metformin might interact with CAT via hydrogen bonds. These data suggested that metformin effectively alleviated CCl4-induced oxidative liver injury in mice and these hepatoprotective effects might be associated with CAT.