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

Abstract

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.

• Authors: Z M M Omar, A A-N Ahmed, M H El-Bakry, M A Ahmed, A Hasan
• Journal: Annales pharmaceutiques francaises (Ann Pharm Fr) Vol. 80 Issue 5 Pg. 659-668 (Sep 2022) ISSN: 0003-4509 [Print] France
• PMID: 35093389 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Chemical References

• Antioxidants
• Silymarin
• Metformin
• Carbon Tetrachloride

Topics

• Animals
• Antioxidants (metabolism)
• Carbon Tetrachloride (metabolism, pharmacology, therapeutic use)
• Chemical and Drug Induced Liver Injury (drug therapy, prevention & control)
• Liver (metabolism, pathology)
• Liver Cirrhosis (chemically induced, drug therapy, metabolism)
• Metformin (pharmacology, therapeutic use)
• Mice
• Oxidative Stress
• Silymarin (metabolism, pharmacology, therapeutic use)