title: Developing effective countermeasures against acute hydrogen sulfide intoxication: challenges and limitations.
abstract: Hydrogen sulfide (H2 S) is a chemical hazard in the gas and farming industry. As it is easy to manufacture from common chemicals, it has also become a method of suicide. H2 S exerts its toxicity through its high affinity with metalloproteins, such as cytochrome c oxidase and possibly via its interactions with cysteine residues of various proteins. The latter was recently proposed to acutely alter ion channels with critical implications for cardiac and brain functions. Indeed, during severe H2 S intoxication, a coma, associated with a reduction in cardiac contractility, develops within minutes or even seconds leading to death by complete electromechanical dissociation of the heart. In addition, long-term neurological deficits can develop owing to the direct toxicity of H2 S on neurons combined with the consequences of a prolonged apnea and circulatory failure. Here, we review the challenges impeding efforts to offer an effective treatment against H2 S intoxication using agents that trap free H2 S, and present novel pharmacological approaches aimed at correcting some of the most harmful consequences of H2 S intoxication.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania.
authors.forename: Philippe
authors.initials: P
authors.lastname: Haouzi
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sonobe
authors.affiliation: Heart and Vascular Institute, Department of Medicine, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania.
authors.forename: Annick
authors.initials: A
authors.lastname: Judenherc-Haouzi
mesh_terms: D000818:Animals; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000506:poisoning / Q000633:toxicity*; D007700:Kinetics; D008751:Methylene Blue / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D008751:Methylene Blue; D006862:Hydrogen Sulfide
keywords: H2S; apnea; hydrogen sulfide; hydroxocobalamin; methemoglobin; methylene blue; pulseless electrical activity