PROTECTIVE ROLE OF S-ADENOSYL-L-METHIONINE AGAINST ACETAMINOPHEN INDUCED MORTALITY AND HEPATOTOXICITY IN MICE

Acetaminophen toxicity is demonstrated to he related to the protein binding of a reactive metabolite formed by the action of a P450 mixed function oxidase. Results of the present study indicate that S-adenosyl-l-methionine (SAMe) protects against mortality induced by high doses (710 mg/kg) of acetaminophen. The liver toxicity induced by acetaminophen also appears to be reduced by SAMe, as shown both by GOT and GPT plasma activities and by histologic observation of the liver. The results of experiments on in vivo and in vitro binding of the radioactivity from acetaminophen to liver microsomal proteins suggest that SAMe protection is related to its metabolism to thiol derivatives in the transmethylation-trans-sulfuration pathway. © 1979.