Studies on the mechanism of toxicity of the mycotoxin, sporidesmin. I. Generation of superoxide radical by sporidesmin.

Sporidesmin (SDMS2), the mycotoxin responsible for 'facial eczema' in ruminants, contains a disulphide group which appears to be intimately involved in its toxic action. The reduced (dithiol) form of sporidesmin has been shown readily to undergo autoxidation in vitro in a reaction which generates superoxide radical (O2-). The autoxidation reaction, which takes place over a wide pH range, is strongly catalysed by trace amounts of copper, although the reaction was inhibited at high concentrations of this metal. Inhibition of the autooxidation of reduced sporidesmin (SDM(SH)2) was also observed in the presence of nickel, cobalt and manganese. Superoxide radical is also generated from SDMS2 itself in a cyclic reduction/autoxidation reaction with glutathione and other thiols; in view of the known toxicity of superoxide and its derivatives, it is suggested that oxygen-free-radicals may be involved in the initiation of the deleterious effects of the mycotoxin.