The influence of gender on metabolic activity of enzymatic system of cytochrome P450 in the model of isolated perfused rat liver.
| Authors | |
|---|---|
| Year of publication | 2006 |
| Type | Article in Proceedings |
| Conference | Final Program and Book of abstracts.Central/East European CINP Regional Meeting |
| MU Faculty or unit | |
| Citation | |
| Field | Pharmacology and pharmaceutical chemistry |
| Keywords | cytochrome P450; influence of gender; isolated perfused liver |
| Description | 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 Samples of perfusate were withdrawn at the 30th, 60th and 120th min of perfusion.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. |
| Related projects: |