Identification of human and rabbit cytochromes P450 1A2 as major isoforms involved in thiabendazole 5-hydroxylation
| Autor: | K. Mace, Pierre Galtier, Michel Alvinerie, A. M. A. Pfeifer, G. Larrieu, Myriam Coulet, Mauro Dacasto, Jean-François Sutra, C. Eeckhoutte |
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| Přispěvatelé: | Unité de recherche Pharmacologie-Toxicologie (UPT), Institut National de la Recherche Agronomique (INRA) |
| Rok vydání: | 1998 |
| Předmět: |
Male
drug-drug interactions thiabendazole metabolism cytochromes P450 hepatocytes human cell lines [SDV]Life Sciences [q-bio] Bronchi Biology Hydroxylation Isozyme Mixed Function Oxygenases chemistry.chemical_compound Species Specificity beta-Naphthoflavone Cytochrome P-450 CYP1A2 medicine Animals Humans Pharmacology (medical) Clofibrate Enzyme Inhibitors Cells Cultured Pharmacology Anticholesteremic Agents CYP1A2 Cytochrome P450 Epithelial Cells Metabolism In vitro Isoenzymes Liver Biochemistry chemistry Enzyme Induction biology.protein Phenobarbital Rabbits medicine.drug |
| Zdroj: | Fundamental and Clinical Pharmacology Fundamental and Clinical Pharmacology, Wiley, 1998, pp.225-235 |
| ISSN: | 1472-8206 0767-3981 |
| Popis: | This report characterized one of the major cytochrome P450 isozyme involved in thiabendazole metabolism. This study was undertaken by using both cultured rabbit hepatocytes treated or not with drugs known to specifically induced various cytochromes P450 isoenzymes (i.e., P450 1A1/2 by beta-naphthoflavone, P450 2B4 by phenobarbital, P450 3A6 by rifampicine and P450 4A by clofibrate) and human liver (THLE-5) and bronchial (BEAS-2B) epithelial cells expressing or not the major constitutive human cytochromes P450 (i.e., CYP1A2, 2A6, 2B6, 2C9, 2D6, 2E1 or 3A4). Only hepatocytes exposed to beta-naphthoflavone and clofibrate significantly metabolized thiabendazole to 5-hydroxythiabendazole. Extensive biotransformation of this anthelmintic only occurred in human cells expressing CYP1A2. Moreover, experiments performed on rabbit preparations showed good correlations between thiabendazole 5-hydroxylase activity and both ethoxyresorufin and methoxyresorufin O-dealkylase activities. Thus, CYP1A2 is a major isoenzyme involved in thiabendazole 5-hydroxylation. |
| Databáze: | OpenAIRE |
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