Scientific reports, 2016-02, Vol.6 (1), p.20831, Article 20831
2016
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- Autor(en) / Beteiligte
- Titel
- Hydrogen Sulfide--Mechanisms of Toxicity and Development of an Antidote
- Ist Teil von
- Scientific reports, 2016-02, Vol.6 (1), p.20831, Article 20831
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/srep20831Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4753484
- Format
- –
- Schlagworte
- Animals, Antidotes - pharmacology, Apoptosis, Brain - drug effects, Brain - metabolism, Carbon monoxide, Cell Differentiation, Cobamides - pharmacology, Drosophila melanogaster, Electron transport, Electron Transport Complex IV - metabolism, F2-Isoprostanes - antagonists & inhibitors, F2-Isoprostanes - metabolism, Fibroblasts - cytology, Fibroblasts - drug effects, Fibroblasts - metabolism, Humans, Hydrogen sulfide, Hydrogen Sulfide - antagonists & inhibitors, Hydrogen Sulfide - toxicity, Hydroxyl Radical - antagonists & inhibitors, Hydroxyl Radical - metabolism, Hydroxyl radicals, Induced Pluripotent Stem Cells - cytology, Induced Pluripotent Stem Cells - drug effects, Induced Pluripotent Stem Cells - metabolism, Isoprostanes, Male, Mice, Mice, Inbred C57BL, Mitochondria, Mitochondria, Heart - drug effects, Mitochondria, Heart - metabolism, Myocardium - metabolism, Neurons - cytology, Neurons - drug effects, Neurons - metabolism, Oxidative Stress, Pluripotency, Poisoning, Potassium Cyanide - antagonists & inhibitors, Potassium Cyanide - toxicity, Rats, Reactive oxygen species, Respiration, Rodents, Stem cells, Sulfide, Sulfides - antagonists & inhibitors, Sulfides - toxicity, Toxicity, Vitamin B12