Role of cellular superoxide dismutase against reactive oxygen metabolite–induced cell damage in cultured rat hepatocytes

✍ Scribed by Yasuaki Ito; Hideyuki Hiraishi; Mahnaz Razandi; Akira Terano; Takashi Harada; Kevin J. Ivey

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 975 KB
• Volume: 16
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840160136

✦ Synopsis

Reactive oxygen metabolites have been reported to be important in the pathogeneeis of ischemia/reJperfusion-induced and alcohol-and druginduced liver injuries. We investigated the role of superoxide diemutase, cellular and extracellular, in preventing reactive oxygen metabolite-induced cyto- toxicityin culturedrat hepatocytes. Cells were exposed to reactive oxygen metabolites enzymatically generated by hypoxanthine-xanthine oxidase. Cytotoxicity was quantified by measuring 51Cr release from prelabeled cells and lactate dehydrogenase release. Reactive oxyppn metabolites caused dose-dependent cytotoxicity. Good correlation was found between the values for W r and lactate dehydmgenase release. Reactive oxygen metaboliteinduced cell damage was reduced by catalase but not by superoxide dismutase. Cellular superoxide dismutase and catalase activities were not increased after incubation with exogenous superoxide dismutase and catalase for up to 5 hr.

Pretreatment with diethyldithiocarbamate inhibited cellular superoxide dismutase activity without inhibiting other antioxidants such as catalase, glutathione, glutathione reductase and glutathione peroxidase and sensitized cells to reactive oxygen metaboliteinduced cytotoxicity. We conclude that hydrogem peroxide is an important mediator in hypoxanthine-xanthine oxi-induced cell damage and that supemside dismutase plays a critical role in cellular antioxidant defeagainst hypoxanthine-xanthine oxidinduced cytotoxicity in cultured rat hepatocytes in vitro. ( m A m L O G Y 1992;16247-264.)

Reactive oxygen metabolites may be critical factors in ischemialreperfusion-induced (1-6) and alcohol- (7)(8)(11)