Novel Insights Into Hydrogen Sulfide–Mediated Cytoprotection

Abstract

Hydrogen sulfide (H₂S) is a colorless, water soluble, flammable gas that has the characteristic smell of rotten eggs. Like other members of the gasotransmitter family (nitric oxide and carbon monoxide), H₂S has traditionally been considered to be a highly toxic gas and environmental hazard. However, much like for nitric oxide and carbon monoxide, the initial negative perception of H₂S has evolved with the discovery that H₂S is produced enzymatically in mammals under normal conditions. As a result of this discovery, there has been a great deal of work to elucidate the physiological role of H₂S. H₂S is now recognized to be cytoprotective in various models of cellular injury. Specifically, it has been demonstrated that the acute administration of H₂S, either prior to ischemia or at reperfusion, significantly ameliorates in vitro or in vivo myocardial and hepatic ischemia-reperfusion injury. These studies have also demonstrated a cardioprotective role for endogenous H₂S. This review article summarizes the current body of evidence demonstrating the cytoprotective effects of H₂S with an emphasis on the cardioprotective effects. This review also provides a detailed description of the current signaling mechanisms shown to be responsible for these cardioprotective actions. Antioxid. Redox Signal. 12, 1203–1217.