Background: Inhibition of hepatic fibrosis is an attainable objective in managing the chronic liver
disease. The present study aimed to investigate possible defensive effects of metformin on the activities of antioxidant
enzymes, hydroxyproline content, and biochemical factors in bile duct ligation (BDL)-induced cholestatic
rats. The interactive behavior of metformin with glutathione peroxidase (GPx) enzyme was also explained by
molecular docking and conformation characterization.
Methods: The present study was conducted on 28-adult male Wistar rats classified into four 7-animal groups:
sham-control, mere BDL, and BDL+ metformin that received daily metformin as gavage in two doses of 250 and
500 mg/kg bw for 10 days. Biochemical analysis, hydroxyproline content, and antioxidant enzymes activity were
Results: The hydroxyproline content significantly increased, but the GPx enzyme activity significantly decreased
in the hepatic tissue following BDL, indicating that an oxidative stress-related model in rats was successfully
constituted. Administration of metformin at two doses attenuated hydroxyproline content in the cholestatic liver
and ameliorated the depletion of GPx enzyme activities compared to the non-treated BDL group (P-value ≤ 0.05).
Molecular docking study provides the evidence for metformin ability to regulate enzymatic activity of GPx.
Conclusion: The research data indicated that due to novel hepatoprotective effects of metformin in an animal
model with BDL-induced liver injury, it was a potential beneficial therapeutic agent for treating the cholestatic
liver disease. The main mechanism might contribute to antioxidant actions, particularly via GPx enzyme.