ZAHRADNÍKOVÁ, Lucia, Ondřej ZENDULKA, Jan JUŘICA and Eva HADAŠOVÁ. The influence of gender on metabolic activity of enzymatic system of cytochrome P450 in the model of isolated perfused rat liver. In Final Program and Book of abstracts.Central/East European CINP Regional Meeting. Tallin: University of Tartu, 2006, p. 84-85.
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Basic information
Original name The influence of gender on metabolic activity of enzymatic system of cytochrome P450 in the model of isolated perfused rat liver.
Name in Czech Vliv pohlaví na metabolicou aktivitu enzymatickeho systemu cytochromu P450 na modele izolovaných perfundovaných jater
Authors ZAHRADNÍKOVÁ, Lucia, Ondřej ZENDULKA, Jan JUŘICA and Eva HADAŠOVÁ.
Edition Tallin, Final Program and Book of abstracts.Central/East European CINP Regional Meeting, p. 84-85, 2 pp. 2006.
Publisher University of Tartu
Other information
Original language English
Type of outcome Proceedings paper
Field of Study 30104 Pharmacology and pharmacy
Country of publisher Estonia
Confidentiality degree is not subject to a state or trade secret
Organization unit Faculty of Medicine
Keywords in English cytochrome P450; influence of gender; isolated perfused liver
Tags cytochrome P450, influence of gender, isolated perfused liver
Tags International impact, Reviewed
Changed by Changed by: PharmDr. Lucia Zendulková Zahradníková, Ph.D., učo 169480. Changed: 7/12/2006 15:02.
Abstract
Interindividual variability in the activity of oxidative and conjugating enzymes, especially within the system of cytochrome P450, can be based on many different factors i.e. gender, age, or interactions between simultaneously applied drugs. A suitable model for investigations on the activity of hepatic CYPs 450 and biotransformation processes is represented by the isolated perfused liver. We studied the influence of gender on selected isoenzymes using the following drugs as specific markers: tolbutamide for CYP2C6, dextromethorphan for CYP2D2, phenacetin for CYP1A2 and nifedipine for CYP3A4. The experiment was carried out on male and female Wistar rats. The recirculating perfusion apparatus was manufactured according to the principle originated by Hugo Sachs GmbH. One of the specific markers – tolbutamide (10.0 mg/l), dextromethorphan (10.0 mg/l), midazolam (10.0 mg/l) or nifedipine (125,0 mg/l) was added as a bolus into the perfusion solution. Samples of perfusate were withdrawn at the 30th, 60th and 120th min of perfusion. Quantitative analysis was performed by HPLC methods . CYP2D2 activity in rat females was significantly higher than in males. Also the final concentration of a marker metabolite (dextrorphan) in females was higher only in CYP2D2. The elevation was 10% in the 60th min and 9% in the 120th min. In contrast activity in CYP subfamily in females was lower than in males. All last three isoforms of CYP450, CYP2C6 (tolbutamid), CYP1A2 (phenacetin) and CYP3A4 (nifedipine), showed lower activity when compared to CYP2D2, and female metabolization rate was slower than in males.
Abstract (in Czech)
Cieľom predkladaného experimentu bolo bližšie charakterizovať vplyv pohlavia na metabolickú aktivitu klinicky najvýznamnejších izoforiem cytochrómu P-450 : CYP1A, CYP2C a CYP2D. Výsledky ukázali, že aktivita CYP2D2 u samíc je signifikantne vyššia než u samcov (v 30. min. zvýšená o 5.7%, v 60. min. o 33% a v 120. min. o 34%). Ako u jedinej nami sledovanej izoformy bola výsledná koncentrácia metabolitu dextrometorfanu- dextrorfanu pri izoforme CYP2D2 vyššia u samíc než u samcov. Ostatné dve izoformy cytochrómu P-450, kde boli ako markre použité pri izoforme CYP2C6 – tolbutamid (sledovaným metabolitom bol 4-hydroxytolbutamid) a CYP1A2 – fenacetin (sledovaným metabolitom bol paracetamol) prejavili v našom experimente oproti izoforme 2D2 výrazne nižšiu aktivitu, pričom samice metabolizovali pomalšie ako samci u oboch nami sledovaných typov enzýmu. Na základe nami získaných výsledkov môžeme tvrdiť, že aktivita metabolických izoenzýmov bola len v jednom prípade vyššia u samíc (metabolizovali touto cestou rýchlejšie) než u samcov. Týkalo sa to izoformy CYP2D2. Pri ostatných dvoch nami sledovaných izoformách (CYP2C6 a CYP1A2) prejavili potkani kmeňa Wistar oproti izoforme 2D2 výrazne nižšiu aktivitu, pričom samice metabolizovali pomalšie ako samci u oboch nami sledovaných typov enzýmu.
Links
MSM0021622404, plan (intention)Name: Vnitřní organizace a neurobiologické mechanismy funkčních systémů CNS
Investor: Ministry of Education, Youth and Sports of the CR, The internal organisation and neurobiological mechanisms of functional CNS systems under normal and pathological conditions.
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