Neurotoxic, inflammatory, and mucosecretory responses in the nasal airways of mice repeatedly exposed to the macrocyclic trichothecene mycotoxin roridin A: dose-response and persistence of injury.

Abstract

Macrocyclic trichothecene mycotoxins encountered in water-damaged buildings have been suggested to contribute to illnesses of the upper respiratory tract. Here, the authors characterized the adverse effects of repeated exposures to roridin A (RA), a representative macrocyclic trichothecene, on the nasal airways of mice and assessed the persistence of these effects. Young, adult, female C57BL/6 mice were exposed to single daily, intranasal, instillations of RA (0.4, 2, 10, or 50 microg/kg body weight [bw]) in saline (50 microl) or saline alone (controls) over 3 weeks or 250 microg/kg RA over 2 weeks. Histopathologic, immunohistochemical, and morphometric analyses of nasal airways conducted 24 hr after the last instillation revealed that the lowest-effect level was 10 microg/kg bw. RA exposure induced a dose-dependent, neutrophilic rhinitis with mucus hypersecretion, atrophy and exfoliation of nasal transitional and respiratory epithelium, olfactory epithelial atrophy and loss of olfactory sensory neurons (OSNs). In a second study, the persistence of lesions in mice instilled with 250 microg/kg bw RA was assessed. Nasal inflammation and excess luminal mucus were resolved after 3 weeks, but OSN loss was still evident in olfactory epithelium (OE). These results suggest that nasal inflammation, mucus hypersecretion, and olfactory neurotoxicity could be important adverse health effects associated with short-term, repeated, airborne exposures to macrocyclic trichothecenes.

• Authors: Kara N Corps, Zahidul Islam, James J Pestka, Jack R Harkema
• Journal: Toxicologic pathology (Toxicol Pathol) Vol. 38 Issue 3 Pg. 429-51 (Apr 2010) ISSN: 1533-1601 [Electronic] United States
• PMID: 20430879 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Macrocyclic Compounds
• Mycotoxins
• Trichothecenes
• roridin A

Topics

• Animals
• Dose-Response Relationship, Drug
• Female
• Immunohistochemistry
• Inflammation (chemically induced, pathology)
• Macrocyclic Compounds (administration & dosage, toxicity)
• Male
• Mice
• Mice, Inbred C57BL
• Mucus (drug effects, metabolism)
• Mycotoxins (administration & dosage, toxicity)
• Nasal Mucosa (drug effects, pathology)
• Rhinitis (etiology)
• Sensory Receptor Cells (drug effects, pathology)
• Trichothecenes (administration & dosage, toxicity)