Perturbation of murine liver cyp-superfamily of isoforms by different combinations of pesticide mixtures
| Autor: | Donatella Canistro, Andrea Sapone, Moreno Paolini, Laura Pozzetti, Alessandra Affatato, R. Barale, Alessandro Stradiotti, Vincenzo Longo, P. Menichini, Massimiliano Broccoli |
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| Přispěvatelé: | Canistro D., Pozzetti L., Sapone A., Broccoli M., Affatato A.A., Stradiotti A., Longo V., Menichini P., Barale R., Paolini M. |
| Rok vydání: | 2008 |
| Předmět: |
Male
Insecticides Cytochrome P450 In Vitro Techniques Pharmacology Toxicology medicine.disease_cause Mice chemistry.chemical_compound Cytochrome P-450 Enzyme System Fenarimol Co-mutagenicity medicine Animals Drug Interactions Vinclozolin Pesticides Pesticide mixture Oxazoles Acephate Chromatography biology Body Weight Organothiophosphorus Compounds General Medicine Metabolism Monooxygenase Fungicides Industrial Isoenzymes Pyrimidines Liver chemistry Enzyme Induction Toxicity biology.protein Phosphoramides Genotoxicity Subcellular Fractions Food Science |
| Zdroj: | Food and chemical toxicology 46 (2008): 34–42. doi:10.1016/j.fct.2007.05.034 info:cnr-pdr/source/autori:Canistro, D.; Pozzetti, L.; Sapone, A.; Broccoli, M.; Affatato, A. A.; Stradiotti, A.; Longo, V.; Menichini, P.; Barale, R.; Paolini, M./titolo:Perturbation of murine liver cyp-superfamily of isoforms by different combinations of pesticide mixtures/doi:10.1016%2Fj.fct.2007.05.034/rivista:Food and chemical toxicology/anno:2008/pagina_da:34/pagina_a:42/intervallo_pagine:34–42/volume:46 |
| ISSN: | 0278-6915 |
| DOI: | 10.1016/j.fct.2007.05.034 |
| Popis: | it was previously found that fenarimol, vinclozolin or acephate, three of the most used pesticides worldwide, provoked a marked perturbation of murine cytochrome P450 (CYP)-linked monooxygenases. Here, to more closely mimic human exposure, it was investigated whether different pesticide combinations administered i.p. in male Swiss Albino CD1 mice in single or repeated fashion (daily, for three consecutive days), affect CYP-dependent oxidations. The four simulated mixtures showed a complex pattern of CYP induction and suppression, especially after repeated injection. For example, while fenarimol alone was the most inducing agent - reaching a 79-fold increase over control in testosterone 2 alpha-hydroxylase - followed by vinclozolin and acephate, coadministration with the former markedly reduced induction. Coadministration with vinclozolin, determined various positive and negative modulations. An increase of CYP2B1/2 and CYP3A1/2-associated oxidases and a decrease of ethoxycoumarin metabolism was observed in the acephate and vinclozolin mixture. An equivalent or reduced CYP expression, if compared to double combinations, was seen using the complete mixture. Taken as a whole, the unpredictability of the recorded effects with simple mixtures, shrinks the misleading extrapolation performed on a single pesticide. If reproduced in human, such changes, altering either endogenous metabolism or biotransformation of ubiquitous toxins, might have public health implications. (c) 2007 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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