Prevention of hydrogen sulfide (H2 S)-induced mouse lethality and cytotoxicity by hydroxocobalamin (vitamin B12a )

• Published in: Toxicology (Amsterdam) Vol. 242; no. 1; pp. 16 - 22
• Main Authors: Truong, Don H, Mihajlovic, Aleksandra, Gunness, Patrina, Hindmarsh, Wayne, O’Brien, Peter J
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 05.12.2007; Amsterdam Elsevier Science
• Subjects: Animals; Antidotes - pharmacology; Antidotes - therapeutic use; Biological and medical sciences; Catalase - metabolism; Cell Survival - drug effects; Cell-Free System - drug effects; Cell-Free System - metabolism; Chemical and industrial products toxicology. Toxic occupational diseases; Cobalt - pharmacology; Cobalt - therapeutic use; Detoxification; Dose-Response Relationship, Drug; Emergency; Environmental Pollutants - metabolism; Environmental Pollutants - toxicity; Gas, fumes; Hepatocytes; Hepatocytes - drug effects; Hydrogen sulfide; Hydrogen Sulfide - metabolism; Hydrogen Sulfide - toxicity; Hydroxocobalamin; Hydroxocobalamin - pharmacology; Hydroxocobalamin - therapeutic use; In Vitro Techniques; Lethal Dose 50; Male; Medical sciences; Mice; Oxidation-Reduction; Oxygen - metabolism; Poisoning - etiology; Poisoning - prevention & control; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Sulfides - metabolism; Sulfides - toxicity; Time Factors; Toxicology; Vitamin B 12a; Vitamin B Complex - pharmacology; Vitamin B Complex - therapeutic use; Hydrogen sulfide; Hydroxocobalamin; Vitamin B 12a; Hepatocytes; Detoxification; Toxic gas; Poison withdrawal; Digestive system; Liver; Rodentia; Cytotoxicity; B-Vitamins; Prevention; Vertebrata; Mammalia; Hepatocyte; Mouse; Animal; Vitamin B12a
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2007.09.009

Abstract Recently, H2 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 B12a ) as an antidote against H2 S poisoning. More than 60% of the mice administered 35 mg/kg (0.63 mmol/kg) of NaSH (LD90 ) 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 μM) or cobalt (50–100 μM) also prevented hepatocyte cytotoxicity induced by NaSH (500 μM). 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.