S –Adenosylmethionine Treatment Prevents Carbon Tetrachloride—Induced S –Adenosylmethionine Synthetase Inactivation and Attenuates Liver Injury

Abstract
: Administration of carbon tetrachloride to rats resulted in induction of hepatic fibrosis and a 60% reduction of hepatic S–adenosylmethionine synthetase activity without producing any significant modification of hepatic levels of S–adenosylmethionine synthetase messenger RNA. The reduction of S–adenosylmethionine synthetase activity was corrected by treatment with S–adenosylmethionine (3 mg/kg/day, intramuscularly). Administration of carbon tetrachloride also produced a 45% depletion of liver glutathione (reduced form) that was corrected by S–adenosylmethionine treatment. After the rats received carbon tetrachloride, a 2.3–fold increase in liver collagen was observed; prolyl hydroxylase activity was 2.5 times greater than that seen in controls. These increases were attenuated in animals treated with carbon tetrachloride and S–adenosylmethionine. The attenuation by S–adenosylmethionine treatment of the fibrogenic effect of carbon tetrachloride was associated with a decrease in the number of rats in which cirrhosis developed. (HEPATOLOGY 1992;16:1022-1027.)