Studies on the mechanism of toxicity of the mycotoxin sporidesmin. 2--Evidence for intracellular generation of superoxide radical from sporidesmin.
Formation of hydrogen peroxide, the dismutation product of superoxide radical, has been demonstrated in erythrocytes incubated with the mycotoxin sporidesmin. Erythrocytic thiols, both non-protein and protein-bound, were depleted in the presence of sporidesmin, whilst haemoglobin was oxidized to methaemoglobin. Irreversible haemoglobin oxidation also occurred in these cells, shown by the formation of Heinz bodies; purified haemoglobin likewise suffered oxidative damage when incubated with sporidesmin in the presence of glutathione. Sporidesmin has previously been shown to generate superoxide radical in vitro; the erythrocytic changes induced by the mycotoxin, which are characteristically produced by compounds which generate 'active oxygen' species, suggest that it is also capable of generating this radical intracellularly.
D000818:Animals; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006366:Heinz Bodies / Q000378:metabolism; D006454:Hemoglobins / Q000032:analysis; D006861:Hydrogen Peroxide / Q000097:blood; D066298:In Vitro Techniques; D007211:Indoles / Q000633:toxicity*; D008297:Male; D008706:Methemoglobin / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013173:Sporidesmins / Q000378:metabolism / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D006454:Hemoglobins; D007211:Indoles; D013173:Sporidesmins; D013438:Sulfhydryl Compounds; D013481:Superoxides; D008706:Methemoglobin; D006861:Hydrogen Peroxide; D005978:Glutathione; C001873:sporidesmin