Cytochrome oxidase inhibition induced by acute hydrogen sulfide inhalation: Correlation with tissue sulfide concentrations in the rat brain, liver, lung, and nasal epithelium

• Published in: Toxicological sciences Vol. 65; no. 1; pp. 18 - 25
• Main Authors: DORMAN, David C, MOULIN, Frederic J.-M, MCMANUS, Brian E, MAHLE, Kristen C, JAMES, R. Arden, STRUVE, Melanie F
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 2002
• Subjects: Animals; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Chemical and industrial products toxicology. Toxic occupational diseases; Electron Transport Complex IV - antagonists & inhibitors; Electron Transport Complex IV - drug effects; Electron Transport Complex IV - metabolism; Gas, fumes; Hydrogen Sulfide - administration & dosage; Hydrogen Sulfide - analysis; Hydrogen Sulfide - toxicity; Inhalation Exposure - adverse effects; Inhalation Exposure - analysis; Liver - drug effects; Liver - metabolism; Lung - drug effects; Lung - metabolism; Male; Medical sciences; Nasal Mucosa - drug effects; Nasal Mucosa - metabolism; Rats; Sulfates - analysis; Thiosulfates - analysis; Time Factors; Toxicity Tests, Acute; Toxicology; Hydrogen Sulfides; Rat; Enzyme; Acute; Liver; Lung; Rodentia; Cytochrome-c oxidase; Metabolism toxicity relation; Central nervous system; Inhalation; Toxicokinetics; Tissue; Vertebrata; Sublethal dose; Mammalia; Enzymatic activity; Animal; Nose; Distribution; Oxidoreductases; Kinetics; Brain (vertebrata)
• ISSN: 1096-6080; 1096-0929; 1096-0929
• DOI: 10.1093/toxsci/65.1.18

Hydrogen sulfide (H2S) is an important brain, lung, and nose toxicant. Inhibition of cytochrome oxidase is the primary biochemical effect associated with lethal H2S exposure. The objective of this study was to evaluate the relationship between the concentration of sulfide and cytochrome oxidase activity in target tissues following acute exposure to sublethal concentrations of inhaled H2S. Hindbrain, lung, liver, and nasal (olfactory and respiratory epithelial) cytochrome oxidase activity and sulfide concentrations were determined in adult male CD rats immediately after a 3-h exposure to H2S (10, 30, 80, 200, and 400 ppm). We also determined lung sulfide and sulfide metabolite concentrations at 0, 1.5, 3, 3.25, 3.5, 4, 5, and 7 h after the start of a 3-h H2S exposure to 400 ppm. Lung sulfide concentrations increased during H2S exposure and rapidly returned to endogenous levels within 15 min after the cessation of the 400-ppm exposure. Lung sulfide metabolite concentrations were transiently increased immediately after the end of the 3-h H2S exposure. Decreased cytochrome oxidase activity was observed in the olfactory epithelium following exposure to > or = 30 ppm H2S. Increased olfactory epithelial sulfide concentrations were observed following exposure to 400 ppm H2S. Hindbrain and nasal respiratory epithelial sulfide concentrations were unaffected by acute H2S exposure. Nasal respiratory epithelial cytochrome oxidase activity was reduced following acute exposure to > or = 30 ppm H2S. Liver sulfide concentrations were increased following exposure to > or = 200 ppm H2S and cytochrome oxidase activity was increased following inhalation exposure to > or = 10 ppm H2S. Our results suggest that cytochrome oxidase inhibition is a sensitive biomarker of H2S exposure in target tissues, and sulfide concentrations are unlikely to increase postexposure in the brain, lung, or nose following a single 3-h exposure to < or = 30 ppm H2S.