Action of methotrexate on cytochrome P-450 monooxygenases in rats
| Autor: | Jean-Louis Rivière, F Gerard, Jérôme Guitton, J.L. Brazier, G Souillet, R. Guilluy |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Administration Oral Pharmacology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cytochrome P-450 Enzyme System Oral administration medicine Animals Pharmacology (medical) Rats Wistar Aminopyrine 030304 developmental biology Breath test Carbon Isotopes 0303 health sciences Unspecific monooxygenase biology medicine.diagnostic_test Cytochrome P450 Monooxygenase Rats 3. Good health Methotrexate Breath Tests chemistry 030220 oncology & carcinogenesis Aminophenazone Microsomes Liver Oxygenases Microsome biology.protein Chemical and Drug Induced Liver Injury Injections Intraperitoneal Aminopyrine N-Demethylase medicine.drug |
| Zdroj: | European Journal of Drug Metabolism and Pharmacokinetics. 19:119-124 |
| ISSN: | 2107-0180 0378-7966 |
| DOI: | 10.1007/bf03188832 |
| Popis: | The aim of this work was to study the action of methotrexate on the cytochrome P-450 hepatic monooxygenases and to follow the evolution of the metabolic processes with time, after oral and intra-peritoneal administration of these drugs to rats. In order to perform this study, we used a new technique the [13C]-aminopyrine breath test (ABT). At the end of the in vivo study, the rats were sacrificed and the cytochrome P-450 concentration as well as microsomal enzymatic activities of aminopyrine N-demethylase, 7-ethoxyresorufin desalkylase, 7-ethoxycoumarin desalkylase, 7-pentoxyresorufin desalkylase were determined. A histological study of the liver was also carried out. Finally, haematological and biochemical parameters were also determined. In this study, 3 series of 6 rats were used: a control group, a group receiving 70 mg/kg of methotrexate by intra-peritoneal route, and a group of rats treated orally with 1 mg/kg of methotrexate every 2 days. For each observation, the variation of the ABT scores and of the cytochrome P-450 amounts as well as the microsomal aminopyrine N-demethylase activity were in good agreement. |
| Databáze: | OpenAIRE |
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