Novel Insights Into Hydrogen Sulfide–Mediated Cytoprotection

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.