S-adenosylmethionine treatment prevents carbon tetrachloride-induced S-adenosylmethionine synthetase inactivation and attenuates liver injury.
Corrales F, Gimenez A, Alvarez L, Caballeria J, Pajares MA, Andreu H, Pares A, Mato JM, Rodes J.
Instituto de Investigaciones Biomedicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
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.
Alcoholic liver disease: new insights in pathogenesis lead to new treatments.
Lieber CS.
Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center and Mount Sinai School of Medicine, NY 10468, USA.
[email protected]
Much progress has been made in the understanding of the pathogenesis of alcoholic liver disease, resulting in improvement of prevention and therapy, with promising prospects for even more effective treatments. The most successful approaches that one can expect to evolve are those that deal with the fundamental cellular disturbances resulting from excessive alcohol consumption. Two pathologic concepts are emerging as particularly useful therapeutically. Whereas it continues to be important to replenish nutritional deficiencies, when present, it is crucial to recognize that because of the alcohol-induced disease process, some of the nutritional requirements change. This is exemplified by methionine, which normally is one of the essential amino acids for humans, but needs to be activated to S-adenosylmethionine (SAMe), a process impaired by the disease.
Thus, SAMe rather than methionine is the compound that must be supplemented in the presence of significant liver disease. Indeed, SAMe was found to attenuate mitochondrial lesions in baboons, replenish glutathione, and significantly reduce mortality in patients with Child A or B cirrhosis.
