Modulation of cellular antioxidant defense activities by sodium arsenite in human fibroblasts.
Many studies have shown that oxygen radicals can be produced during arsenic metabolism. We report here that in human fibroblasts (HFW cells) sodium arsenite exposure caused increased formation of fluorescent dichlorofluorescein (DCF) by oxidation of the nonfluorescent form. The enhanced DCF fluorescence was inhibited by a radical scavenger, butylated hydroxytoluene. The effects of sodium arsenite treatment on cellular antioxidant activities were then examined. Treatment of HFW cells with sodium arsenite resulted in a significant increase in heme oxygenase activity and ferritin level. Sodium arsenite-enhanced heme oxygenase synthesis was inhibited by co-treatment of cells with the antioxidants sodium azide and dimethyl sulfoxide. Furthermore, sodium arsenite treatment did not apparently affect glucose-6-phosphate dehydrogenase activity, but resulted in significantly increased glutathione levels and superoxide dismutase activity, slightly decreased glutathione peroxidase activity, and significantly decreased catalase activity. Sodium arsenite toxicity was partly reduced by addition of catalase to the culture medium. These results imply that arsenite can enhance oxidative stress in HFW cells.
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
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D018053:Arsenites / Q000378:metabolism / Q000633:toxicity*; D001386:Azides / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005293:Ferritins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D009153:Mutagens / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D019810:Sodium Azide; D017670:Sodium Compounds / Q000378:metabolism / Q000633:toxicity*; D013439:Sulfhydryl Reagents / Q000378:metabolism / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism
D018053:Arsenites; D001386:Azides; D003470:Culture Media; D005452:Fluoresceins; D009153:Mutagens; D017670:Sodium Compounds; D013439:Sulfhydryl Reagents; C029569:diacetyldichlorofluorescein; C017947:sodium arsenite; D005293:Ferritins; D019810:Sodium Azide; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D006419:Heme Oxygenase (Decyclizing); D013482:Superoxide Dismutase; D005978:Glutathione; D004121:Dimethyl Sulfoxide