Cytotoxic mechanisms of hydrosulfide anion and cyanide anion in primary rat hepatocyte cultures

Toxicology
Rodney W ThompsonWilliam M Valentine

Abstract

Hydrogen sulfide and hydrogen cyanide are known to compromise mitochondrial respiration through inhibition of cytochrome c oxidase and this is generally considered to be their primary mechanism of toxicity. Experimental studies and the efficiency of current treatment protocols suggest that H(2)S may exert adverse physiological effects through additional mechanisms. To evaluate the role of alternative mechanisms in H(2)S toxicity, the relative contributions of electron transport inhibition, uncoupling of mitochondrial respiration, and opening of the mitochondrial permeability transition pore (MPTP) to hydrosulfide and cyanide anion cytotoxicity in primary hepatocyte cultures were examined. Supplementation of hepatocytes with the glycolytic substrate, fructose, rescued hepatocytes from cyanide anion induced toxicity, whereas fructose supplementation increased hydrosulfide anion toxicity suggesting that hydrosulfide anion may compromise glycolysis in hepatocytes. Although inhibitors of the MPTP opening were protective for hydrosulfide anion, they had no effect on cyanide anion toxicity, consistent with an involvement of the permeability transition pore in hydrosulfide anion toxicity but not cyanide anion toxicity. Exposure of isol...Continue Reading

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Citations

Mar 13, 2013·Archives of Toxicology·Sanae KannoToshiji Mukai
Aug 3, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kunihiro SuzukiCsaba Szabo
Sep 4, 2012·Biochimica Et Biophysica Acta·Fatemeh ShakiJalal Pourahmad
Jul 23, 2011·Toxicology Mechanisms and Methods·Praveen N Dube, Basaling B Hosetti
Apr 19, 2011·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Na WuFengtong Hao
Oct 12, 2013·Acta Cirúrgica Brasileira·Rondon Tosta RamalhoPedro Carvalho Cassino
Mar 20, 2010·Toxicology and Industrial Health· Sahar Ali Farahat, Nirmeen Adel Kishk
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Aug 29, 2019·Scandinavian Cardiovascular Journal : SCJ·Yuko IshikawaToji Yamazaki
Oct 26, 2005·The Journal of Experimental Biology·David JulianStephanie E Wohlgemuth
Sep 15, 2021·European Journal of Clinical Investigation·Inês Mateus, Carina Prip-Buus
Sep 7, 2019·The Science of the Total Environment·Guoqiang ZhaoQunqun Liu

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