S-adenosylmethionine treatment prevents carbon tetrachloride—induced S-adenosylmethionine synthetase inactivation and attenuates liver injury

✍ Scribed by Fernando Corrales; América Giménez; Luis Alvarez; Joan Caballería; María A. Pajares; Hernán Andreu; Albert Parés; Professor José M. Mato; Joan Rodés

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 738 KB
• Volume: 16
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840160427

✦ Synopsis

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 2.6 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 asso- ciated with a decrease in the number of rats in which cirrhosis developed. (HEPATOLOGY 1992;16 1022-1027.)

Liver injury is associated with impaired methionine metabolism (1). A delay in the clearance of plasma methionine after its systemic administration to patients with liver damage has been observed (2, 3). Because about half the methionine is metabolized by the liver (1, 41, where it is mainly converted into S-adenosylmethionine (SAM) by the enzyme S A M synthetase, impaired hepatic synthesis and utilization of SAM is suggested in liver injury. Indeed, decreased S A M synthetase activity in liver biopsy specimens from cirrhotic patients has been observed (5-7). Similarly, hepatic S A M depletion has been detected in galactosamine-induced and buthionine sulfoximinc+