Hydrogen Sulfide--Mechanisms of Toxicity and Development of an Antidote
| Autor: | Jiang, J, Chan, A, Ali, S, Saha, A, Haushalter, KJ, Lam, WLMR, Glasheen, M, Parker, J, Brenner, M, Mahon, SB, Patel, HH, Ambasudhan, R, Lipton, SA, Pilz, RB, Boss, GR |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Antidotes Induced Pluripotent Stem Cells Apoptosis Sulfides Inbred C57BL Electron Transport Complex IV Mice Animals Humans Hydrogen Sulfide Potassium Cyanide Nutrition Neurons F2-Isoprostanes Hydroxyl Radical Myocardium Neurosciences Brain Heart Cell Differentiation Fibroblasts Stem Cell Research Mitochondria Rats Other Physical Sciences Oxidative Stress Drosophila melanogaster Biochemistry and Cell Biology Cobamides |
| Zdroj: | Scientific reports, vol 6, iss 1 Jiang, J; Chan, A; Ali, S; Saha, A; Haushalter, KJ; Lam, WLMR; et al.(2016). Hydrogen Sulfide-Mechanisms of Toxicity and Development of an Antidote. Scientific Reports, 6. doi: 10.1038/srep20831. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/9k95f0s4 |
| DOI: | 10.1038/srep20831. |
| Popis: | 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 F 2-isoprostanes in brains and hearts of mice. The vitamin B 12 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. |
| Databáze: | OpenAIRE |
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