Toxicity of thiols and disulphides: involvement of free-radical species.

Sulphur is essential to life, and thiols and disulphides play essential roles in cellular biochemistry. Such compounds are also widely distributed in the food of man and his domestic animals, and they are extensively used in industry. However, many thiols and disulphides have been shown to be toxic. Aliphatic, aromatic, and heterocyclic compounds of this type are haemolytic agents in animals while aminothiols have been shown to induce many cytotoxic effects in vitro and the epidithiodioxopiperazine mycotoxin, sporidesmin, is a potent hepatotoxic agent. Structure-activity relationships among these compounds and factors which modulate their harmful effects are consistent with a toxic mechanism involving redox cycling between the thiol and the corresponding disulphide. Thiyl radicals and "active oxygen" species are formed in this process, and it is suggested that these substances are responsible for initiating the tissue damage provoked by thiols and disulphides.