Cytochrome oxidase inhibition induced by acute hydrogen sulfide inhalation: correlation with tissue sulfide concentrations in the rat brain, liver, lung, and nasal epithelium.
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.
Dorman
David C
DC
CIIT Centers for Health Research, 6 Davis Drive, PO Box 12137, Research Triangle Park, North Carolina 27709-2137, USA. dorman@ciit.org
Moulin
Frederic J-M
FJ
McManus
Brian E
BE
Mahle
Kristen C
KC
James
R Arden
RA
Struve
Melanie F
MF
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity*; D019570:Inhalation Exposure / Q000009:adverse effects* / Q000032:analysis; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013431:Sulfates / Q000032:analysis; D013885:Thiosulfates / Q000032:analysis; D013997:Time Factors; D023382:Toxicity Tests, Acute
D013431:Sulfates; D013885:Thiosulfates; D003576:Electron Transport Complex IV; D006862:Hydrogen Sulfide