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3-methylindole induces transient olfactory mucosal injury in ponies
M A Miller1, S J Kottler, J A Ramos-Vara
1UMC Veterinary Medical Diagnostic Laboratory, PO Box 6023, Columbia, MO 65205, USA. millerma@missouri.edu
Abstract:
Response to 3-methylindole (3MI) varies among species. Mice recover from 3MI-induced bronchiolar epithelial injury but sustain persistent olfactory mucosal injury with scarring and epithelial metaplasia. In contrast, 3MI induces obliterative bronchiolitis in horses and ponies, but olfactory mucosal injury has not been reported. To evaluate the effect of 3MI on equine olfactory mucosa, ponies were dosed orally with 100 mg 3MI/kg (n = 9) or corn oil vehicle (n = 6). All ponies treated with 3MI developed obliterative bronchiolitis with mild olfactory injury. By 3 days after 3MI dosing, olfactory epithelium appeared disorganized with decreased and uneven surface height and scalloping of the basement membrane zone. Epithelial cells of Bowman's glands were hypertrophic. Proliferation of olfactory epithelium and Bowman's glands was supported by an increased mitotic index and positive immunohistochemical staining for proliferating cell nuclear antigen as compared with controls. The activity of 11beta-hydroxysteroid dehydrogenase, an olfactory mucosal cytosolic enzyme localized to sustentacular and Bowman's glandular epithelial cells, was concurrently decreased. By 9 days postdosing, olfactory mucosal lesions had lessened. Results indicate that 3MI transiently injures equine olfactory mucosa without the extensive necrosis, scarring, or metaplasia seen in murine olfactory mucosa or in equine bronchiolar epithelium.
Insights
3-methylindole (3MI) causes temporary damage to the olfactory mucosa in ponies, unlike the permanent injury seen in mice. This study investigated 3MI
Area of Science:
- Veterinary Pathology
- Toxicology
- Equine Respiratory and Olfactory Health
Background:
- 3-methylindole (3MI) causes varied species-specific responses.
- Mice experience olfactory mucosal injury after 3MI exposure, while horses develop obliterative bronchiolitis.
- Equine olfactory mucosal response to 3MI is not well-documented.
Purpose of the Study:
- To investigate the effects of 3-methylindole (3MI) on equine olfactory mucosa.
- To compare equine olfactory response to 3MI with known responses in mice and equine bronchiolar epithelium.
Main Methods:
- Ponies were administered 3MI orally (100 mg/kg) or a corn oil vehicle.
- Olfactory mucosal tissues were analyzed for morphological changes, cell proliferation (PCNA), and enzyme activity (11beta-HSD).
- Histological and immunohistochemical analyses were performed at specific time points post-dosing.
Main Results:
- All 3MI-treated ponies developed obliterative bronchiolitis and mild olfactory mucosal injury.
- Olfactory epithelium showed disorganization, basement membrane scalloping, and hypertrophic Bowman's glands.
- Increased cell proliferation and decreased 11beta-hydroxysteroid dehydrogenase activity were observed in the olfactory mucosa.
Conclusions:
- 3-methylindole (3MI) causes transient injury to equine olfactory mucosa.
- The equine olfactory response differs from the persistent injury observed in mice.
- Lesions in equine olfactory mucosa resolved by 9 days post-dosing, indicating a temporary effect.
