Sulfane Sulfur in Toxicology: A Novel Defense System Against Electrophilic Stress

Electrophiles can undergo covalent modification of cellular proteins associated with its dysfunction, thereby exerting toxicity. Small nucleophilic molecules such as glutathione protect cells from electrophilic insult by binding covalently to electrophiles to form adducts that are excreted into the extracellular space. Recent studies indicate that sulfane sulfur, which is defined as a sulfur atom with 6 valence electrons and no charge, plays an essential role in protection against electrophile toxicity because sulfane sulfur can be highly nucleophilic compared to the corresponding thiol group. Advances in the development of assays to detect sulfane sulfur have revealed that sulfane sulfur-containing molecules such as persulfide/polysulfide species are ubiquitous in cells and tissues. Also, there is growing evidence that the binding of sulfane sulfur to electrophiles forms sulfur adducts as detoxified metabolites. Although the biosynthesis pathways of sulfane sulfur are known, its regulatory function in toxicology is still unclear. This review outlines the current knowledge of the synthesis, chemical properties, detection methods, interactions with electrophiles, and toxicological significance of sulfane sulfur, as well as suggesting directions for future research.