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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 F\n                    <jats:sub>2<\/jats:sub>\n                    -isoprostanes in brains and hearts of mice. The vitamin B\n                    <jats:sub>12<\/jats:sub>\n                    analog cobinamide reversed the cellular toxicity of sulfide and rescued\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1038\/srep20831","type":"journal-article","created":{"date-parts":[[2016,2,15]],"date-time":"2016-02-15T05:54:28Z","timestamp":1455515668000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":238,"title":["Hydrogen Sulfide\u2014Mechanisms of Toxicity and Development of an Antidote"],"prefix":"10.1038","volume":"6","author":[{"given":"Jingjing","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameh","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arindam","family":"Saha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristofer J.","family":"Haushalter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai-Ling Macrina","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Glasheen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Parker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sari B.","family":"Mahon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemal H.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Ambasudhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart A.","family":"Lipton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate B.","family":"Pilz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerry R.","family":"Boss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,15]]},"reference":[{"key":"BFsrep20831_CR1","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1146\/annurev.pa.32.040192.000545","volume":"32","author":"RJ Reiffenstein","year":"1992","unstructured":"Reiffenstein, R. 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