title: Protection of S-adenosyl methionine against the toxicity of clivorine on hepatocytes.
abstract: 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 (5μM) prevented the cytotoxicity of clivorine on human normal liver L-02 cells. DNA fragmentation assay showed that SAM (5μM) improved clivorine-induced L-02 cell apoptosis, and the results of Western blot showed that SAM (5μM) 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 100μM) of clivorine for 48h, cellular GSH was decreased in a concentration-dependent manner, while SAM (5μM) enhanced 50μM clivorine decreased cellular GSH. Further MTT assay showed that 5mM GSH and 5mM 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.
authors.affiliation: Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China; Shanghai R&D Centre for Standardization of Chinese Medicines, Shanghai 201203, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ji
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang