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Induction of olfactory mucosal and liver metabolism of lidocaine by 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin
Author(s) -
Genter Mary Beth,
Apparaju Sandhya,
Desai Pankaj B.
Publication year - 2002
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.10032
Subject(s) - olfactory mucosa , mucous membrane of nose , drug metabolism , nasal administration , xenobiotic , pharmacology , metabolite , nasal cavity , enzyme , lidocaine , metabolism , drug , respiratory mucosa , medicine , chemistry , olfactory system , biochemistry , immunology , anesthesia , lung , psychiatry , surgery
Formulation of drugs for administration via the nasal cavity is becoming increasingly common. It is of potential clinical relevance to determine whether intranasal drug administration itself, or exposure to other xenobiotics, can modulate the levels and/or activity of nasal mucosal metabolic enzymes, thereby affecting the metabolism and disposition of the drug. In these studies, we examined changes in several of the major metabolic enzymes in nasal epithelial tissues upon exposure to the environmental contaminant 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin (TCDD), as well as the impact of these changes on the metabolism of a model intranasally administered drug, lidocaine. Results of these studies show that TCDD can induce multiple metabolic enzymes in the olfactory mucosa and that the pattern of induction in the olfactory mucosa does not necessarily parallel that which occurs in the liver. Further, increases in enzyme levels noted by Western blot analysis were associated with increased activities of several nasal mucosal enzymes as well as with enhanced conversion of lidocaine to its major metabolite, monoethyl glycine xylidide (MEGX). These results demonstrate that environmental exposures can influence the levels and activity of nasal mucosal enzymes and impact the pharmacology of drugs administered via the nasal route. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:128–134, 2002. DOI 10.1002/jbt.10032

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