Studies on the mechanism of toxicity of the mycotoxin sporidesmin. 3--Inhibition by metals of the generation of superoxide radical by sporidesmin.
The mycotoxin sporidesmin has previously been shown to generate superoxide radical. This reaction involves autoxidation of the reduced form of the mycotoxin, a dithiol. In the present study, a number of mercaptide-forming metals have been shown to inhibit superoxide formation from sporidesmin in vitro. Furthermore, these metals decreased the rate of sporidesmin-induced hydrogen peroxide formation in erythrocytes and ameliorated the subsequent oxidative damage to these cells. These effects were found to be specific to sporidesmin; mercaptide-forming metals did not inhibit the changes induced by compounds which are not dependent upon thiol groups for active oxygen generation. Zinc was one of the most potent inhibitors of superoxide generation from sporidesmin in these test systems; only mercury and cadmium were significantly more active. Salts of zinc are known to provide effective protection against the harmful effects of sporidesmin in vivo. The results of these studies provide a possible explanation for this effect.
D000818:Animals; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000097:blood; D006861:Hydrogen Peroxide / Q000097:blood; D066298:In Vitro Techniques; D007211:Indoles / Q000633:toxicity*; D008670:Metals / Q000494:pharmacology*; D009183:Mycotoxins / Q000633:toxicity*; D010084:Oxidation-Reduction; D051381:Rats; D013173:Sporidesmins / Q000633:toxicity*; D013481:Superoxides / Q000378:metabolism*
D007211:Indoles; D008670:Metals; D009183:Mycotoxins; D013173:Sporidesmins; D013481:Superoxides; D006861:Hydrogen Peroxide; D005978:Glutathione; C001873:sporidesmin