Effects of S-adenosylmethionine on lipid peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis

Background/Aim: The aim of this study was to investigate the effects of S-adenosylmethionine on liver peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis. Methods: Cirrhosis was induced in three groups of six rats by repeated injections of carbon tetrachloride over 9 weeks, One group of animals was treated only with carbon tetrachloride, and the other two received carbon tetrachloride plus S-adenosylmethionine (10 mg/kg intramuscularly daily) from week 3 to week 9, and from week 6 to week 9 of the study, respectively, Two additional groups of six rats, a control group and a group treated only with S-adenosylmethionine, were also studied, Glutathione concentration, thiobarbituric acid-reactive substances, collagen content, prolyl hydroxylase activity, and procollagen type I mRNA expression were determined in liver samples. Results: All carbon tetrachloride-treated rats had cirrhosis at the end of the study, Cirrhosis was also present in five of the six carbon tetrachloride-treated rats receiving S-adenosylmethionine for 3 weeks, but in only one of the six rats that received S-adenosylmethionine for 6 weeks, Hepatic glutathione was significantly diminished in carbon tetrachloride-treated rats (2.7+/-0.3 mu mol/g tissue) and returned to normal in rats receiving S-adenosylmethionine for 3 or 6 weeks (3.7+/-0.13 and 3.9+/-0.11 mu mol/g tissue, respectively), The hepatic thiobarbituric acid-reactive substances were significantly lower in rats treated with carbon tetrachloride and S-adenosylmethionine for 6 weeks (98+/-5 mmol/g) than in rats treated with carbon tetrachloride (134+/-12 nmol/g) acid in those treated with carbon tetrachloride and S-adenosylmethionine for 3 weeks (127+/-13 nmol/g), There were no differences in either hepatic collagen and prolyl hydroxylase activity between rats that received only carbon tetrachloride and those treated with S-adenosylmethionine for 3 weeks, In contrast, carbon tetrachloride-treated rats receiving S-adenosylmethionine for 6 weeks had significantly lower collagen and prolyl hydroxylase activity than the other two groups, A much greater increase in procollagen type I mRNA was found in carbon tetrachloride-treated rats than in rats treated,vith carbon tetrachloride and S-adenosylmethionine for 6 weeks, Furthermore, there was a significant correlation between the hepatic thiobarbituric acid-reactive substances and prolyl hydroxylase activity and hepatic collagen. Conclusions: We conclude that the early administration of S-adenosylmethionine in a model of carbon tetrachloride-induced liver injury restores glutathione levels and reduces lipid peroxidation, resulting in less advanced liver fibrosis.