TY - JOUR
T1 - Developing effective countermeasures against acute hydrogen sulfide intoxication
T2 - challenges and limitations
AU - Haouzi, Philippe
AU - Sonobe, Takashi
AU - Judenherc-Haouzi, Annick
N1 - Funding Information:
The authors are grateful to Ms. Nicole Tubbs for her skillful technical assistance. This work has been supported by the CounterACT Program, National Institutes of Health Office of the Director (NIH OD), and the National Institute of Neurological Disorders and Stroke (NINDS), Grant numbers 1R21NS080788-01 and 1R21NS090017-01. Some of the studies reported in this review were also supported by the National Center for Research Resources and the National Center for Advancing Translational Science, National Institutes of Health, through Grant UL1TR000127.
Publisher Copyright:
© 2016 New York Academy of Sciences.
PY - 2016
Y1 - 2016
N2 - Hydrogen sulfide (H2S) 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. H2S 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 H2S 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 H2S 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 H2S intoxication using agents that trap free H2S, and present novel pharmacological approaches aimed at correcting some of the most harmful consequences of H2S intoxication.
AB - Hydrogen sulfide (H2S) 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. H2S 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 H2S 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 H2S 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 H2S intoxication using agents that trap free H2S, and present novel pharmacological approaches aimed at correcting some of the most harmful consequences of H2S intoxication.
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U2 - 10.1111/nyas.13015
DO - 10.1111/nyas.13015
M3 - Review article
C2 - 26945701
AN - SCOPUS:84983483300
VL - 1374
SP - 29
EP - 40
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
SN - 0077-8923
IS - 1
ER -