Hydrogen sulfide as a potent scavenger of toxicant acrolein.

Acrolein (ACR) is a metabolic byproduct in vivo and a ubiquitous environmental toxicant. It is implicated in the initiation and development of many diseases through multiple mechanisms, including the induction of oxidative stress. Currently, our understanding of the body defense mechanism against ACR toxicity is still limited. Given that hydrogen sulfide (HS) has strong antioxidative actions and it shares several properties of ACR scavenger glutathione (GSH), we, therefore, tested whether HS could be involved in ACR detoxification. Taking advantage of two cell lines that produced different levels of endogenous HS, we found that the severity of ACR toxicity was reversely correlated with HS-producing ability. In further support of the role of HS, supplementing cells with exogenous HS increased cell resistance to ACR, whereas inhibition of endogenous HS sensitized cells to ACR. In vivo experiments showed that inhibition of endogenous HS with CSE inhibitor markedly increased mouse susceptibility to the toxicity of cyclophosphamide and ACR, as evidenced by the increased mortality and worsened organ injury. Further analysis revealed that HS directly reacted with ACR. It promoted ACR clearance and prevented ACR-initiated protein carbonylation. Collectively, this study characterized HS as a presently unrecognized endogenous scavenger of ACR and suggested that HS can be exploited to prevent and treat ACR-associated diseases.