THE INFLUENCE OF POLYPHENOLIC EXTRACT FROM ANDRE AND BLAUER PORTUGAISER GRAPE BYPRODUCTS ON THE ACTIVITY OF LIVER CYP1A2 ISOENZYME

Authors

ZENDULKA Ondřej ZAHRADNÍKOVÁ Lucia JUŘICA Jan TOTUŠEK Jiří

Year of publication 2007
Type Article in Periodical
Magazine / Source Biomedical Papers
MU Faculty or unit

Faculty of Medicine

Citation
Field Pharmacology and pharmaceutical chemistry
Keywords polyphenolic extracts; wine byproducts; isolated perfused rat liver
Description The enzymatic system of cytochrome P 450 (CYP450) is one of the most important enzymatic systems participating in drug metabolism. Both, the induction and inhibition of specific CYP450 isoenzymes are important in terms of the efficacy or toxicity of drugs that are substrates for this system. Within the genetic polymorphism as an essential definition of activity of CYP450 many other factors influence liver oxidative metabolism (i.e. age, sex, administered drugs, diseases). Nutrition state, components of diet and exposure to chemical elements belongs to the most important exogenous ones. Polyphenolic compounds are biologically active substances with many protective effects. As well as other components of diet polyphenols can also influence the activity of liver CYP450 and can interfere with administered drugs metabolized by hepatic isoenzymes of CYP450. The aim of our present study was to investigate the influence of polyphenolic extract from grape byproducts and hypercholesterolemic diet on the activity of hepatic CYP 1A2 isoenzyme in rats. As we predicted, hypercholesterolemic diet had no effect on the activity of hepatic CYP1A2. Our opinion is that the only effect of long-lasting hypercholesterolemic diet on the activity of CYP can be caused by steatosis of hepatocytes and thus a decrease of their metabolic activity. Administration of polyphenolic extract caused induction of CYP1A2 isoenzyme and was manifested as increased levels of paracetamol (PAR) in perfusion medium. One should expect that inducers of CYP isoenzyme would cause in the treated animals an increase in metabolite levels and decrease of marker levels compared to the controls. In our case however administration of polyphenolic extract lead to statistically significant increase of both, PAR and phenacetine (PHEN) in the 30th minute of perfusion. In our opinion, this can be caused by the changes in the binding capacity of liver for PHEN, as liver of control rats showed rather a big portion of PHEN bound, too.
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