Trans-resveratrol enhances sex differences in CYP1A2 metabolic activity in rats

Authors

ZENDULKA Ondřej ZAHRADNÍKOVÁ Lucia JUŘICA Jan TOTUŠEK Jiří

Year of publication 2008
Type Article in Periodical
Magazine / Source Prague Medical Report
MU Faculty or unit

Faculty of Medicine

Citation
Field Pharmacology and pharmaceutical chemistry
Keywords trans-resveratrol; quercetin; cytochrome P-450
Description Trans-resveratrol (tRES) is a polyphenolic compound present in a variety of plants. TRes elicits many actions in human body which are considered to be protective. Some authors reported tRES influence on the activity of cytochrome P450 (CYP450). It is one of the major enzymatic systems. Many substances including drugs are metabolized by CYP450. Its activity depends on many factors e.g. genotype, age, sex, or xenobiotics. Changes in CYP450 activity can play an important role in drug effectiveness and toxicity, thus knowledge of xenobiotic influence on this enzyme is important for predicting drug interactions. The aim of our study was to evaluate the influence of sex difference and tRES administration on activity of CYP1A2 in rats. Male and female Wistar albino rats were used. Animals weighing 200g were housed under controlled conditions with free access to food and water. Animals were divided into 4 groups. Two groups were males and two females. Resveratrol premedicated male (RM) and female (RF) animals were administered intraperitoneally by tRES dissolved 30% DMSO at the dose of 5mg/kg/day for 10 days. Control female (CF) and male (CM) rats were administered by i.p. injections of 30% DMSO in an appropriate volume. We used model of isolated perfused rat liver for analysis of CYP1A2 activity. The recirculating apparatus was constructed according to the principles of Miller. Marker phenacetine (PHE) (10.0 mg/l) was added into the perfusion medium. Samples were collected at the 30th, 60th and 120th min of perfusion. Quantitative analysis was performed by HPLC using method described by Juřica. Our results documented influence of sex on the CYP450 activity. Levels of PAR were significantly increased in CF group (p<0.05), which means that females metabolized PHE faster than males (CM). The activity of CYP1A2 in tRES rats was similar to control animals. TRES did not influence the activity in animals of same sex, but interestingly enhanced the sexual difference. PAR in perfusate of tRES females was significantly higher than in tRES males. This result is similar to that found in control animals, but statistical significance of this effect was p<0,001. We confirmed our suggestion, that tRES can modulate activity of CYP1A2 in dependence of sex. Our hypothesis was based on the estrogenic effect of tRES. Our opinion is that estrogenic mechanism of CYP450 modulation is the crucial factor of differences in sex dependent CYP450 activity.
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