Activation of the Glutathione Peroxidase by Metformin in the Bile-duct Ligation induced Liver Injury: In vivo Combined with Molecular Docking Studies.
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 also determined.


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.
['Mansourian|Mahboubeh|M|', 'Sadeghi|Hossein|H|', 'Doustimotlagh|Amir Hossein|AH|']
D000818:Animals D001652:Bile Ducts D004195:Disease Models, Animal D004305:Dose-Response Relationship, Drug D005979:Glutathione Peroxidase D007004:Hypoglycemic Agents D008026:Ligation D008107:Liver Diseases D008297:Male D008687:Metformin D062105:Molecular Docking Simulation D018384:Oxidative Stress D051381:Rats D017208:Rats, Wistar
glutathione peroxidase metformin Bile-duct ligation in vivo antioxidant enzymes hydroxyproline cholestasis molecular docking.