Hydrogen Sulfide—Mechanisms of Toxicity and Development of an Antidote

Abstract

Hydrogen sulfide is a highly toxic gas-second only to carbon monoxide as a cause of inhalational deaths. Its mechanism of toxicity is only partially known, and no specific therapy exists for sulfide poisoning. We show in several cell types, including human inducible pluripotent stem cell (hiPSC)-derived neurons, that sulfide inhibited complex IV of the mitochondrial respiratory chain and induced apoptosis. Sulfide increased hydroxyl radical production in isolated mouse heart mitochondria and F2-isoprostanes in brains and hearts of mice. The vitamin B12 analog cobinamide reversed the cellular toxicity of sulfide, and rescued Drosophila melanogaster and mice from lethal exposures of hydrogen sulfide gas. Cobinamide worked through two distinct mechanisms: direct reversal of complex IV inhibition and neutralization of sulfide-generated reactive oxygen species. We conclude that sulfide produces a high degree of oxidative stress in cells and tissues, and that cobinamide has promise as a first specific treatment for sulfide poisoning.

DOI: 10.1038/srep20831

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05010020162017
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Cite this paper

@inproceedings{Jiang2016HydrogenSO, title={Hydrogen Sulfide—Mechanisms of Toxicity and Development of an Antidote}, author={Jingjing Jiang and Adriano Chan and Sameh S Ali and Arindam Saha and Kristofer J. Haushalter and Wai-Ling Macrina Lam and Megan Glasheen and James Parker and Matthew W. Brenner and Sari Brenner Mahon and Hemal Patel and Rajesh Ambasudhan and Stuart A. Lipton and Renate B. Pilz and Gerry R. Boss}, booktitle={Scientific reports}, year={2016} }