title: 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.affiliation: Comparative Medicine and Integrative Biology, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Kara N
authors.initials: KN
authors.lastname: Corps
authors.forename: Zahidul
authors.initials: Z
authors.lastname: Islam
authors.forename: James J
authors.initials: JJ
authors.lastname: Pestka
authors.forename: Jack R
authors.initials: JR
authors.lastname: Harkema
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D047028:Macrocyclic Compounds / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009093:Mucus / Q000187:drug effects* / Q000378:metabolism; D009183:Mycotoxins / Q000008:administration & dosage / Q000633:toxicity*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000473:pathology; D012220:Rhinitis / Q000209:etiology*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000473:pathology; D014255:Trichothecenes / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D047028:Macrocyclic Compounds; D009183:Mycotoxins; D014255:Trichothecenes; C038849:roridin A