Chronic dexamethasone treatment potentiates insult to olfactory receptor cells produced by 3-methylindole

The effect of chronic dexamethasone treatment on damage to olfactory recept or cells produced by 3-methylindole (3-MI) was examined. Twelve rats were i njected, 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 differ ent rats, from 1 to 4 weeks after a single intraperitoneal administration o f 150 mg/kg 3-MI. One, two, three, and four weeks after exposure to 3-MI, d ifferent groups of rats, three specimens per each treatment condition, rece ived bilateral application of horseradish peroxidase to the olfactory mucos a and were subsequently sacrificed. Anterograde labeling of primary afferen ts, i.e., an inverse correlate of the degree of cellular damage, was quanti tatively 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 w eeks, respectively. The corresponding values in the dexamethasone-treated r ats were 15.7, 29.7, 87.5, and 110.5. The MOD values of the dexamethasone-i njected rats were significantly lower than those of the saline-injected rat s for post-3-MI weeks 1 and 2, indicative of stronger damage to olfactory r eceptor 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 induci ng action of dexamethasone on the cytochrome P450 responsible for metabolic bioactivation of 3-MI. (C) 1999 Elsevier Science B.V. All rights reserved.