Metformin versus silymarin as hepatoprotective agents in mice fibrotic model caused by carbon tetrachloride

Objectives. - To study metformin hepatoprotective effects compared to silymarin on hepatic fibrosis caused by carbon tetrachloride (CCl4) in mice.Material and methods. - Liver fibrosis in mice was achieved by intraperitoneal injection of 2 mL/kg of CCl4 dilution in olive oil [1:9 (v/v)] twice a week for 7 weeks followed by oral treatment with metformin (250 mg/kg/day) or silymarin (100 mg/kg/day) (a standard hepato-protective drug). The changes that follow liver fibrosis were assessed by measurement of hepatic enzymes (ALT, AST and ALP), histopathological examination using hematoxylin and eosin stain, special stains, and a-smooth muscle actin (a-SMA) immunostaining, measuring oxidative stress markers (MDA, GSH, NOx and MnSOD) and transforming growth factor-beta 1 (TGF-(31) in liver. Results. - Liver fibrosis was obviously developed in mice after intraperitoneal injection with CCl4 for 7 weeks. Both silymarin and metformin treatment exhibited a significant decrease in the fibrotic changes and similarly an increase in endogenous antioxidants. Interestingly there is a significant difference between silymarin and metformin regarding both efficacy and potency.Conclusion. - These findings highlight the anti-inflammatory, antioxidant and antifibrotic effects of metformin in CCl4-induced hepatic fibrosis in mice, but silymarin is more beneficial.(c) 2022 Acad acute accent emie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.