Methods for Suppressing Hydrogen Sulfide in Biological Systems.

Significance: Hydrogen sulfide (H2S) plays critical roles in redox biology, and its regulatory effects are tightly controlled by its cellular location and concentration. The imbalance of H2S is believed to contribute to some pathological processes. Recent Advances: Downregulation of H2S requires chemical tools such as inhibitors of H2S-producing enzymes and H2S scavengers. Recent efforts have discovered some promising inhibitors and scavengers. These advances pave the road toward better understanding of the functions of H2S. Critical Issues: Precise H2S downregulation is challenging. The potency and specificity of current inhibitors are still far from ideal. H2S-producing enzymes are involved in complex sulfur metabolic pathways and ubiquitously present in biological matrices. The inhibition of these enzymes can cause unwanted side effects. H2S scavengers allow targeted H2S clearance, but their options are still limited. In addition, the scavenging process often results in biologically active by-products. Future Directions: Further development of potent and specific inhibitors for H2S-producing enzymes is needed. Scavengers that can rapidly and selectively remove H2S while generating biocompatible by-products are needed. Potential therapeutic applications of scavengers and inhibitors are worth exploring. Antioxid. Redox Signal. 36, 294-308.