Induction of hepatic CYP2B1/2 by a teratogenic compound cis-1-[-4-(p-menthane-8-yloxy)phenyl]piperadine (YM9429) in rats
| Autor: | Masakatsu Shibata, Takemi Yoshida, Yoshihiko Funae, Satoshi Numazawa, Susumu Imaoka |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Cytochrome Biology Pharmacology Toxicology Cytochrome P-450 Enzyme System Piperidines Oral administration medicine Animals Rats Wistar Cytochrome P450 Rats Teratogens Mechanism of action Enzyme Induction Toxicity Cytochrome P-450 CYP2B1 Steroid Hydroxylases biology.protein Microsomes Liver Phenobarbital Aryl Hydrocarbon Hydroxylases medicine.symptom Benzphetamine Drug metabolism medicine.drug |
| Zdroj: | The Journal of toxicological sciences. 25(1) |
| ISSN: | 0388-1350 |
| Popis: | A teratogenic compound cis-1-[-4-(p-menthane-8-yloxy)phenyl]piperadine (YM9429)selectively induces skeletal malformations characterized by cleft palate in rat fetuses. In the present study, we investigated the effect of YM9429 on hepatic cytochrome P-450s and their activities in rats. Oral administrations of YM9429 at a dose of 250, 500 or 750 mg / kg daily for 3 days induced cytochrome P-450 contents in a dose-dependent manner. Concomitant induction of enzyme activities of benzphetamine N-demethylase, erythromycin N-demethylase and, to a lesser extent, aminopyrine N-demethylase was observed. Immunoblot analysis revealed that YM9429 up-regulated hepatic levels of CYP2B1 / 2 and CYP3A1 / 2 proteins. A single dose of YM9429 at 250 mg / kg induced CYP2B1 / 2 protein levels significantly. These results suggest that YM9429 is a strong inducer of cytochrome P-450 with characteristics resembling those of phenobarbital. |
| Databáze: | OpenAIRE |
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