6533b7d5fe1ef96bd1264da5

RESEARCH PRODUCT

Activity and expression of drug metabolizing enzymes in olfactory mucosa of rats treated by hepatic inducers

subject

description

International audience; Several drug-metabolizing enzymes (DME), such as cytochrome P450- dependent monooxygenases (CYP) and transferases have been characterized in the olfactory epithelium. Some of them are preferentially expressed in this tissue, while others are similar to those present in the liver. The role of these enzymes remains unclear. Since the olfactory mucosa is in direct contact with the external environment, these enzymes can contribute to the detoxification of chemical compounds. In addition, these enzymes could be involved in the olfaction process, especially in the biotransformation of odorants. Indeed, the rapid inactivation and clearance of odorants is a prerequisite for the capability of the olfactory system to receive iterative incoming signals. If such a hypothesis is plausible,it can be assumed that induction or inhibition of DME would have an impact on clearance of odorants and therefore on the olfactory signal. The aim of the present study was to identify treatments which modulate olfactory DME in the rat. The effects of known inducers of hepatic DME (arochlor, dexamethasone,phenobarbital, methylcholanthrene and ethoxyquin) on activity and mRNA expression of a panel of DME have been evaluated.All these treatments caused changes in activity and expression of several DME in the olfactory mucosa. The effects were found to be lower than those observed in the liver. Administration of dexamethasone resulted in significant increases in CYP-dependent activities and in CYP2G1 and CYP3A9 expression in the olfactory mucosa. Significant induction of UDP-glucuronosyltransferase (UGT) activities and UGT2A1 expression was also observed after dexamethasone treatment. Ethoxyquin administration induced a significant enhancement of quinone reductase and a decrease of CYP-dependent activities. The other treatments(arochlor, phenobarbital, methylcholanthrene) slightly increased the activities of UGT and quinone reductase. This study demonstrated that it is possible to modulate drug-metabolizing enzymes in the rat olfactory mucosa by chemical treatments.The impact of dexamethasone and ethoxyquin on olfactory signal will be further investigated.