Protective Effects of S-Adenosylmethionine against CCl4- and Ethanol-Induced Experimental Hepatic Fibrosis

摘要

In this study the effects of S-adenosylmethionine (SAM) on experimental hepatic fibrotic rats induced by carbon tetrachloride (CCl4) and ethanol and the relevant potential mechanisms were explored. Hepatic fibrotic rat models were established with CCl4 diluted in olive oil being drunk with 10% ethanol in water. SAM was used both for prevention and treatment. Histological evaluation was carried out by hematoxylin-eosin (HE) and Masson staining of hepatic samples. Serum biochemical assays showed that alanine aminotransferase (ALT) was increased and albumin (ALB) was decreased by CCl4 and ethanol, and both effects were suppressed by preventing and treating use of SAM. The model control rats got significantly higher scores in fatty degeneration, lobular inflammation, and hepatocyte ballooning. A significant improvement was observed in the SAM-prevented rats and SAM-treated rats, which was consistent with the change of fibrosis scoring in each group. Smad3 was induced by CCl4 and ethanol in the model control group, which was significantly down regulated by SAM. SAM reduced both total Smad3 and phospho-Smad3 in vitro. SAM had a protective effect on hepatic fibrosis in rats induced by CCl4 combined with ethanol and the down-regulation of activity and expression of Smad3 were involved in the potential mechanisms.