Studies on the mechanism of toxicity of the mycotoxin sporidesmin. IV. Inhibition by copper-chelating agents of the generation of superoxide radical by sporidesmin.

Sporidesmin, the mycotoxin responsible for "facial eczema" in ruminants, has previously been shown to generate superoxide free radical, the latter being formed during autoxidation of the reduced form of the mycotoxin, a dithiol. The autoxidation of reduced sporidesmin is catalysed by iron and by copper, although cobalt, nickel, manganese, cerium, vanadium and molybdenum were found to be without effect. The catalytic activity of copper was some 900-fold that of iron. Cyanide and certain organic complexing agents inhibit superoxide production from reduced sporidesmin by virtue of their ability to chelate copper. Some proteins behave likewise, again through binding of the metal catalyst, although amino acid-bound copper was found to be as effective as ionic copper in catalysing the autoxidation reaction. From the results of the present experiments, it is suggested that any superoxide production from sporidesmin in vivo would be mediated by the intracellular transport pool of copper. Furthermore, the ability of zinc to inhibit intestinal absorption of copper may be involved in the mechanism whereby salts of this metal afford protection against the harmful effects of sporidesmin in the living animal.