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 with carbon tetrachloride, and the other two received carbon tetrachloride plus S-adenosyl-methionine (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 received 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 μmol/g tissue) and returned to normal in rats received S-adenosylmethionine for 3 or 6 weeks (3.7±0.13 and 3.9±0.11 μmol/g tissue, respectively). The hepatic thiobarbituric acid-reactive substances were significantly lower in rats treated with carbon tetrachloride and S-adenosyl-methionine for 6 weeks (98±5 nmol/g) than in rats treated with carbon tetrachloride (134±12 nmol/g) and 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 received 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 with 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.