title: Olfactory mucosal necrosis in male CD rats following acute inhalation exposure to hydrogen sulfide: reversibility and the possible role of regional metabolism.
abstract: Hydrogen sulfide (H2S) is a potent inhibitor of cytochrome oxidase (CO) and is associated with dysosmia and anosmia in humans and nasal lesions in exposed rodents. An improved understanding of the pathogenesis of these lesions is needed to determine their toxicological relevance. We exposed 10-week-old male CD rats to 0, 30, 80, 200, or 400 ppm H2S for 3 hours/day for 1 or 5 days consecutively. The nose was histologically examined 24 hours after H2S exposure, and lesion recovery was assessed at 2 and 6 weeks following the 5-day exposure. A single 3-hour exposure to > or = 80 ppm H2S resulted in regeneration of the respiratory mucosa and full thickness necrosis of the olfactory mucosa localized to the ventral and dorsal meatus, respectively. Repeated exposure to the same concentrations caused necrosis of the olfactory mucosa with early mucosal regeneration that extended from the dorsal medial meatus to the caudal regions of the ethmoid recess. Acute exposure to 400 ppm H2S induced severe mitochondrial swelling in sustentacular cells and olfactory neurons, which progressed to olfactory epithelial necrosis and sloughing. CO immunoreactive cells were more frequently observed in regions of the olfactory mucosa commonly affected by H2S than in regions that were not. These findings demonstrate that acute exposure to >80 ppm H2S resulted in reversible lesions in the respiratory and olfactory mucosae of the CD rat and that CO immunoreactivity may be a susceptibility factor for H2S-induced olfactory toxicity in the rat.
authors.affiliation: CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Karrie A
authors.initials: KA
authors.lastname: Brenneman
authors.forename: David F
authors.initials: DF
authors.lastname: Meleason
authors.forename: Madhabananda
authors.initials: M
authors.lastname: Sar
authors.forename: Marianne W
authors.initials: MW
authors.lastname: Marshall
authors.forename: R Arden
authors.initials: RA
authors.lastname: James
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Gross
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Martin
authors.forename: David C
authors.initials: DC
authors.lastname: Dorman
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D003576:Electron Transport Complex IV / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000633:toxicity*; D008297:Male; D009061:Mouth Mucosa / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003576:Electron Transport Complex IV; D006862:Hydrogen Sulfide