Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
Toxicologic Pathology
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Brenneman, K. A.
Right arrow Articles by Dorman, D. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brenneman, K. A.
Right arrow Articles by Dorman, D. C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Olfactory Mucosal Necrosis in Male CD Rats Following Acute Inhalation Exposure to Hydrogen Sulfide: Reversibility and the Possible Role of Regional Metabolism

Karrie A. Brenneman

CT Centers for Health Research, Research Triangle Park, North Carolina 27709

David F. Meleason

CT Centers for Health Research, Research Triangle Park, North Carolina 27709

Madhabananda Sar

CT Centers for Health Research, Research Triangle Park, North Carolina 27709

Marianne W. Marshall

CT Centers for Health Research, Research Triangle Park, North Carolina 27709

R. Arden James

CT Centers for Health Research, Research Triangle Park, North Carolina 27709

Elizabeth A. Gross

CT Centers for Health Research, Research Triangle Park, North Carolina 27709

Joseph T. Martin

CT Centers for Health Research, Research Triangle Park, North Carolina 27709

David C. Dorman

CT Centers for Health Research, Research Triangle Park, North Carolina 27709, dorman{at}ciit.org

Hydrogen sulfide (H 2S) 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 pathogenesi s 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 ≥80 ppm H 2S 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.

Key Words: Nasal pathology • cytochrome oxidase • annexin I • olfactory marker protein • immunohistochemistry • microvillar cells • mitochondrial swelling • olfactory epithelial regeneration.

References

  • Agency for Toxic Substances and Disease Registry (ATSDR) (1999). Toxicological Profile for Hydrogen Sulfide, US Department of Commerce, Springfield, VA.
  • Boorman GA, Morgan KT, Uriah LC (1990). Nose, larynx, and trachea. In: Pathology of the Fischer Rat, Boorman GA, Eustis SL, Elwell MR, Montgomery CA Jr, MacKenzie WF (eds). Academic Press, Inc, San Diego, p 321.
  • Brenneman KA, James RA, Gross EA, Dorman DC (2000). Olfactory neuronal loss following subchronic inhalation exposure to low levels of hydrogen sulfide in adult male CD rats. Toxicol Pathol 28: 326—333.[Abstract/Free Full Text]
  • Buckley LA, Morgan KT, Swenberg JA, James RA, Hamm Jr JE, Barrow CS (1985). The toxicity of dimethylamine in F-344 rats and B6C3F1 mice following a 1 year inhalation exposure. Fundam Appl Toxicol 5: 341—352.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Carr VM, Farbman AI, Colletti LM, Morgan JI (1991). Identification of a new nonneurona l cell type in the rat olfactory epithelium. Neuroscience 45: 433—449.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Cheville NF (1976). Cell Pathology, The Iowa State University Press, Ames, IA, pp 10, 46—47.
  • Harding JW, Getchell TV, Margolis FLF (1978). Deviation of the primary olfactory pathway in mice. V. Long-term effect of intranasal ZnSO4 irrigation on behavior, biochemistry and morphology. Brain Res 140: 271—285.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Hastings L., Miller ML, Minnerma DJ, Evans J., Radike M. (1991). Effects of methyl bromide on the rat olfactory system. Chem Senses 16: 43—55.[Abstract/Free Full Text]
  • Hirsch AR, Zavala G. (1999). Long term effects on the olfactory system of exposure to hydrogen sulfide. Occup Environ Med 56: 284—287.[Abstract/Free Full Text]
  • Jiang XZ, Buckley LA, Morgan KT (1983). Histopathology of toxic responses to chlorine gas in the nasal passages of rats and mice. Toxicol Appl Pharmacol 103: 143—155.
  • JohnsonEW,EllerPM,JafekBW ( 1993). An immuno-electron microscopic comparison of olfactory marker protein localization in the supranuclear regions of the rat olfactory epithelium and vomeronasal organ neuroepithelium. Acta Otolaryngol 113: 766—771.[Medline] [Order article via Infotrieve]
  • Keller A., Margolis FL (1975). Immunological studies of the rat olfactory marker protein. J Neurochem 24: 1101—1106.[Web of Science][Medline] [Order article via Infotrieve]
  • Khan AA, Schuler MM, Prior MG, Yong S., Coppock RW, Florence LZ, Lillie LE (1990). Effects of hydrogen sulfide exposure on lung mitochondrial respiratory chain enzymes in rats. Toxicol Appl Pharmacol 103: 482—490.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Kimbell JS, Godo MN, Gross EA, Joyner DR, Richardson RB, Morgan KT (1997). Computer simulation of inspiratory airflow in all regions of the F344 rat nasal passages. Toxicol Appl Pharmacol 145: 388—398.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Lopez A., Prior M., Yong S., Lillie L., Lefebvre M. (1988). Nasal lesions in rats exposed to hydrogen sulfide for four hours. Am J Vet Res 49: 1107—1111.[Web of Science][Medline] [Order article via Infotrieve]
  • Méryl S., Gross EA, Joyner DR, Godo M., Morgan KT (1994). Nasal diagrams: A tool for recording the distribution of nasal lesions inrats and mice. Toxicol Pathol 22: 353—372.[Abstract/Free Full Text]
  • Miller ML, Andringa A., Evans JE, Hastings L. (1995). Microvillar cells of the olfactory epithelium: Morphology and regeneration following exposure to toxic compounds. Brain Res 669: 1—9.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Moran DT, Carter Rowley J. III, Jafek BW (1982). Electron microscopy of human olfactory epithelium reveals a new cell type: The microvillar cell. Brain Res 253: 39—46.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Morgan KT (1991). Approaches to the identification and recording of nasal lesions in toxicology studies. Toxicol Pathol 19: 337—351.[Web of Science][Medline] [Order article via Infotrieve]
  • Morgan KT, Monticello TM (1990). Airflow, gas deposition, and lesion distribution in the nasal passages. Environ Health Perspect 85: 209—218.[Web of Science][Medline] [Order article via Infotrieve]
  • National Research Council ( 1996). Guide for the Care and Use of Laboratory Animals, National Academic Press, Washington, DC, p 125.
  • Nicholls, P. (1975). The effect of sulphide on cytochrome aa3 isosteric and allosteric shifts of the reduced {alpha}-peak. Biochim Biophys Acta 396: 24—35.[Medline] [Order article via Infotrieve]
  • Nicholson RA, Roth SH, Zhang A., Zheng J., Brookes J., Skrajny B., Bennington R. (1998). Inhibition of respiratory and bioenergetic mechanisms by hydrogen sulfide in mammalian brain. J Toxicol Environ Health 54:491—507.[CrossRef][Web of Science]
  • Sar M., Welsch F. (1999). Differential expression of estrogen receptor-β and estrogen receptor-{alpha} in the rat ovary. Endocrinology 140: 963—971.[Abstract/Free Full Text]
  • Savolainen H., Tenhunen R., Elovaara E., Tossavainen A. (1980). Cumulative biochemical effects of repeated hydrogen sulfide intoxication in mouse brain. Int Arch Occup Environ Health 46: 87—92.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Schneider JS, Tobe EH, Mozley PD Jr, Barniskis L., Lidsky TI (1998). Persistent cognitive and motor deficits following acute hydrogen sulfide poisoning. Occup Med (Oxf ) 48: 255—260.[Medline] [Order article via Infotrieve]
  • Struve MF, Brisbois JN, James RA, Marshall MW, Dorman DC (2001). Neurotoxicologica l effects associated with short-term exposure of Sprague-Dawley rats to hydrogen sulfide. Neurotoxicology 22: 375—385.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Tvedt B., Skyberg K., Aaserud O., Hebbesland A., Matheisen T. (1991). Brain damage caused by hydrogen sulfide: A follow-up study of six patients. Am J Ind Med 20: 91—101.[Web of Science][Medline] [Order article via Infotrieve]
  • United States Environmental Protection Agency (US EPA) (1993). Health assessment document for hydrogen sulfide, Office of Research and Development, Research Triangle Park, NC.
  • Wong-Riley MTT (1989). Cytochrome oxidase: An endogenous metabolic marker for neuronal activity. Trends Neurosci 12: 94—101.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

Toxicologic Pathology, Vol. 30, No. 2, 200-208 (2002)
DOI: 10.1080/019262302753559533
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Toxicol PatholHome page
E. S. Roberts, R. S. Thomas, and D. C. Dorman
Gene Expression Changes Following Acute Hydrogen Sulfide (H2S)-induced Nasal Respiratory Epithelial Injury
Toxicol Pathol, June 1, 2008; 36(4): 560 - 567.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
J. R. Harkema, S. A. Carey, and J. G. Wagner
The Nose Revisited: A Brief Review of the Comparative Structure, Function, and Toxicologic Pathology of the Nasal Epithelium
Toxicol Pathol, April 1, 2006; 34(3): 252 - 269.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
K. Kai, H. Satoh, T. Kajimura, M. Kato, K. Uchida, R. Yamaguchi, S. Tateyama, and K. Furuhama
Olfactory Epithelial Lesions Induced by Various Cancer Chemotherapeutic Agents in Mice
Toxicol Pathol, October 1, 2004; 32(6): 701 - 709.
[Abstract] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Brenneman, K. A.
Right arrow Articles by Dorman, D. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brenneman, K. A.
Right arrow Articles by Dorman, D. C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?