Protection of S-adenosyl methionine against the toxicity of clivorine on hepatocytes

In this study, we investigated the protective effects of S-adenosyl-l-methionine (SAM), which is a precursor of cellular reduced glutathione (GSH), against the hepatotoxicity of pyrrolizidine alkaloid clivorine. MTT assay showed that SAM (5 μM) prevented the cytotoxicity of clivorine on human normal liver L-02 cells. DNA fragmentation assay showed that SAM (5 μM) improved clivorine-induced L-02 cell apoptosis, and the results of Western blot showed that SAM (5 μM) decreased clivorine-induced caspase-3 activation. Cellular GSH analysis showed that when L-02 cells were exposed to different concentrations (0, 3, 10, 30, 50 and 100 μM) of clivorine for 48 h, cellular GSH was decreased in a concentration-dependent manner, while SAM (5 μM) enhanced 50 μM clivorine decreased cellular GSH. Further MTT assay showed that 5 mM GSH and 5 mM N-acetyl-l-cysteine (NAC) both had protective effects against clivorine-induced hepatotoxicity. Our results suggest that SAM has protective effects against the hepatotoxicity of clivorine possibly by enhancing cellular GSH level and increasing cellular defensive ability against clivorine-induced cytotoxicity.