Toxicological insights into hydrogen sulfide biology in Caenorhabditis elegans: detection, metabolism, and functional outcomes

Hydrogen sulfide (H₂S), while historically recognized as a poisonous substance, also serves as a gasotransmitter that mediates a wide spectrum of physiological processes across species and is involved in the mechanisms of various exogenous toxicants. The Caenorhabditis elegans (C. elegans) is a valuable tool in toxicology, featuring both a conserved enzymatic H₂S metabolic pathway and a unique dietary bacteria-derived H₂S generation mechanism. Notably, existing data demonstrate that H₂S can extend lifespan, strengthen stress resistance, and preserve mitochondrial function in C. elegans. Its molecular mechanisms may be related to regulating HIF-1 and SKN-1 signaling, enhancing deacetylase SIR-2.1 activity, and exerting epigenetic effects, including methylation of histone H3K4 and protein persulfidation. More recently, H₂S has also been utilized to develop novel multi-target drugs for Alzheimer's disease using the C. elegans model. The present review summarizes recent advances in H₂S-based detection, metabolism and its functional outcomes, as well as molecular underpinnings of H₂S effects in C. elegans, offering valuable insight into the potential of this alternative model system for investigating H₂S-related physiological and toxicological mechanisms.