Prevention of hydrogen sulfide (H2S)-induced mouse lethality and cytotoxicity by hydroxocobalamin (vitamin B(12a)).
Recently, H(2)S (an environmental toxin) was proposed to induce cytotoxicity not only by inhibiting cytochrome oxidase but also by generating reactive oxygen species [Truong, D., Eghbal, M., Hindmarsh, W., Roth, Sh., O'Brien, P., 2006. Molecular mechanisms of hydrogen sulfide toxicity. Drug Metab. Rev. 38, 733-744]. In the following, evidence is presented supporting the use of hydroxocobalamin (vitamin B(12a)) as an antidote against H(2)S poisoning. More than 60% of the mice administered 35 mg/kg (0.63 mmol/kg) of NaSH (LD(90)) survived (at 24 h) when hydroxocobalamin (0.25 mmol/kg) was given after NaSH administration whereas less than 15% of the mice survived without hydroxocobalamin. Hydroxocobalamin (50-100 microM) or cobalt (50-100 microM) also prevented hepatocyte cytotoxicity induced by NaSH (500 microM). Furthermore, adding hydroxocobalamin 60 min later than NaSH still showed some protective activity. Catalytic amounts of hydroxocobalamin or cobalt added to a solution containing NaSH caused the disappearance of NaSH and induced oxygen uptake, indicative of NaSH oxidation and Co reduction, respectively.
Truong
Don H
DH
Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada.
Mihajlovic
Aleksandra
A
Gunness
Patrina
P
Hindmarsh
Wayne
W
O'Brien
Peter J
PJ
D000818:Animals; D000931:Antidotes / Q000494:pharmacology* / Q000627:therapeutic use; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System / Q000187:drug effects / Q000378:metabolism; D003035:Cobalt / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects*; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000633:toxicity*; D006879:Hydroxocobalamin / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D011041:Poisoning / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013440:Sulfides / Q000378:metabolism / Q000633:toxicity*; D013997:Time Factors; D014803:Vitamin B Complex / Q000494:pharmacology* / Q000627:therapeutic use
D000931:Antidotes; D004785:Environmental Pollutants; D017382:Reactive Oxygen Species; D013440:Sulfides; D014803:Vitamin B Complex; D003035:Cobalt; D002374:Catalase; C018021:cobaltous chloride; C025451:sodium bisulfide; D006879:Hydroxocobalamin; D010100:Oxygen; D006862:Hydrogen Sulfide