Chronic dexamethasone treatment potentiates insult to olfactory receptor cells produced by 3-methylindole.
The effect of chronic dexamethasone treatment on damage to olfactory receptor cells produced by 3-methylindole (3-MI) was examined. Twelve rats were injected, every other day, with dexamethasone (1.5 mg/kg, i.p.), and 12 rats with saline alone. Injections began 1 week before and continued, in different rats, from 1 to 4 weeks after a single intraperitoneal administration of 150 mg/kg 3-MI. One, two, three, and four weeks after exposure to 3-MI, different groups of rats, three specimens per each treatment condition, received bilateral application of horseradish peroxidase to the olfactory mucosa and were subsequently sacrificed. Anterograde labeling of primary afferents, i.e., an inverse correlate of the degree of cellular damage, was quantitatively determined by measuring the mean optical density (MOD) of staining in sections of the olfactory bulb. In saline-injected rats, the MOD values were 27.0, 46.6, 87.1, and 104.7 for one, two, three, and four post-3-MI weeks, respectively. The corresponding values in the dexamethasone-treated rats were 15.7, 29.7, 87.5, and 110.5. The MOD values of the dexamethasone-injected rats were significantly lower than those of the saline-injected rats for post-3-MI weeks 1 and 2, indicative of stronger damage to olfactory receptor cells in the rats treated with the glucocorticoid. The data suggest that dexamethasone potentiates the 3-MI olfactotoxicity during the first 2 weeks after insult. This effect, at least partly, may be due to the inducing action of dexamethasone on the cytochrome P450 responsible for metabolic bioactivation of 3-MI.
Kratskin
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Smell and Taste Center, Department of Otorhinolaryngology: Head and Neck Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. kratskin@mail.med.upenn.edu
Kimura
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Y
Hastings
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L
Doty
R L
RL
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004357:Drug Synergism; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D009830:Olfactory Bulb / Q000187:drug effects* / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012862:Skatole / Q000009:adverse effects / Q000378:metabolism; D014118:Toxins, Biological / Q000009:adverse effects / Q000378:metabolism
D005938:Glucocorticoids; D014118:Toxins, Biological; D003907:Dexamethasone; D012862:Skatole