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 2mL/kg of CCl4 dilution in olive oil [1:9 (v/v)] twice a week for 7 weeks followed by oral treatment with metformin (250mg/kg/day) or silymarin (100mg/kg/day) (a standard hepatoprotective 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 α-smooth muscle actin (α-SMA) immunostaining, measuring oxidative stress markers (MDA, GSH, NOx and MnSOD) and transforming growth factor-beta 1 (TGF-β1) 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.
Keywords: CCl4; Fibrose hépatique; Liver fibrosis; Metformin; Metformine; Silymarin; Silymarine.
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