S-Adenosylmethionine protects against acetaminophen-induced hepatotoxicity in mice
Abstract
An overdose of acetaminophen (APAP) is the most frequent cause of fulminant liver failure in the United States. Increasing evidence demonstrates that oxidative stress plays an important etiologic role in APAP-induced liver injury. S-Adenosylmethionine (SAMe) is a key intermediate in the hepatic trans-sulfuration pathway and serves as a precursor for glutathione (GSH) as well as the methyl donor in most transmethylation reactions. In the present study, we investigated effects of SAMe on liver injury induced by APAP administration in male C57BL/6 mice. Two related studies were performed. In the first experiment, SAMe (1g/kg BW) was injected intraperitoneally 4 h before APAP (600 mg/kg BW) administration. In the second experiment, SAMe was injected intraperitoneally 1 h after APAP administration. Our results showed that APAP administration induced changes typical of confluent centrilobular necrosis by histological examination and a marked elevation in serum alanine aminotransferase (ALT) activity. APAP administration induced significant decreases in both hepatic and blood SAMe concentrations. In addition, APAP decreased intracellular (both cytosolic and mitochondrial) GSH concentrations along with increased lipid peroxidation in c...Continue Reading