Selenium-dependent glutathione peroxidase inhibitors increase toxicity of prooxidant compounds in chicks

The acute lethality of paraquat (1, 1'-dimethyl-4,4'-bipyridinium dichloride; also methyl viologen) for chicks was reduced in a dose-dependent manner by adding to a selenium-deficient torula-yeast-based diet low concentrations (0.02-0.04 ppm) of selenium (Se) as either Na2SeO3, selenomethionine or a high Se yeast without significantly increasing plasma Se-dependent glutathione peroxidase (Se GSH-Px) activity. Similarly, chicks orally dosed with 100 mg nitrofurantoin [N-(5-nitro-2 furfurylidine)-1-aminohydantoin] per kilogram had highest mortalities in the Se-deficient (unsupplemented) group; lowest mortalities occurred in chicks supplemented with 0.2 ppm Se; chicks supplemented with 0.02 ppm Se survived at rates not statistically different from chicks either unsupplemented or supplemented with 0.2 ppm Se. The activities of SeGSH-px in various vital organs were significantly elevated by supplementation of 0.2 ppm Se to Se-deficient chicks; but only kidney SeGSH-Px increased with 0.02 ppm Se. Additionally, no histopathology was observed in the vital organs of moribund chicks 5 or 24 h following nitrofurantoin administration at any dietary level of Se tested. Exposure of chicks to oxygen enhanced the toxicity of nitrofurantoin, but the protective effect of dietary Se was still evident. Two inhibitors of SeGSH-Px, D(-)-penicillamine X HCl and aurothioglucose, were found to increase the lethalities of both nitrofurantoin and paraquat. Aurothioglucose was most effective when administered simultaneously with the prooxidant compounds; penicillamine increased toxicities only when administered at least 24 h before paraquat or nitrofurantoin (it decreased nitrofurantoin lethality and did not significantly alter paraquat toxicity if given simultaneously). These data support an hypothesis that the protection offered by dietary Se against the acute toxicities of the prooxidant compounds paraquat and nitrofurantoin may be provided by SeGSH-Px in the chick.