3-Methylindole Induces Transient Olfactory Mucosal Injury in Ponies

Abstract

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 ϭ 9) or corn oil vehicle (n ϭ 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 11␤-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.

Intranasal Location and Immunohistochemical Characterization of the Equine Olfactory Epithelium

“…Moreover, Ki-67 expression is widely used for the characterization of the humans, rodents and carnivore OE and both markers are useful to detect dividing cells ( Carter et al, 2004 ; Murdoch and Roskams, 2007 ; Bock et al, 2009 ; Holbrook et al, 2011 ). PCNA expression has already been described for the equine sensory epithelium of the vomeronasal organ ( Miller et al, 2003 ) and was also found in the rat OE (own unpublished data). Typically, PCNA positive cells were found in small groups indicating that proliferating areas intermingle with non-proliferating regions ( Graziadei and Graziadei, 1979 ).…”

“…The globose basal cells are thought to be the progenitors of the ORNs ( Graziadei and Graziadei, 1979 ; Calof and Chikaraishi, 1989 ; Mackay-Sim and Kittel, 1991 ) and the sustentacular cells ( Schwob et al, 1994 ; Chen et al, 2004 ). Due to their proliferative activity, globose basal cells can be visualized by BrdU ( Carter et al, 2004 ) or [ 3 H]-thymidine incorporation ( Graziadei and Graziadei, 1979 ) and express proliferating cell nuclear antigen (PCNA) or Ki-67 ( Miller et al, 2003 ; Carter et al, 2004 ; Bock et al, 2009 ; Holbrook et al, 2011 ). The horizontal basal cells possess features of multipotent stem cells and can induce regeneration after epithelial damage ( Schwartz Levey et al, 1991 ; Holbrook et al, 1995 ; Carter et al, 2004 ; Murdoch and Roskams, 2007 ).…”

Opinion of the Scientific Panel on Animal Health and Welfare (AHAW) on a request from the Commission related to welfare aspects of the castration of piglets

“…Bronchiolar epithelial injury in mice is transient, but olfactory mucosal injury with scarring and metaplasia persists. In contrast, Miller et al (2003) found that 3 days of 100mg skatole/kg in horses resulted in persistent damage (necrosis, scarring and metaplasia) to the bronchiolar epithelium but only transient injury occurred in olfactory mucosa.…”

Theoretical analysis of the effect of intermolecular interaction on ir spectra of skatole

“…Indole derivatives are extremely physiologically active compounds that are widely used in medical practice. They can exert stimulating and inhibiting action on the nervous system and possess hemorrhagic, sedative, and radioprotective properties in addition to others [1,2]. For example, indole-3-carbinol facilitates detoxification of poisons, including those with carcinogenic properties, and reduces the threat of developing a series of hormone-dependent tumors of epithelial origin [3].…”