The influence of diet on metabolic activity of cytochrome P450

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Year of publication 2007
Type Article in Proceedings
Conference WORKSHOP Addiction and Eating Disorders - Neurobiology and Comorbidities
MU Faculty or unit

Faculty of Medicine

Field Pharmacology and pharmaceutical chemistry
Keywords CYP 450; polyphenolic extract; isolated perfused rat liver
Description As we predicted, hypercholesterolemic diet had no effect on the activity of hepatic CYP4501A2 isoenzyme and concentrations of marker PHEN and its metabolite PAR were comparable in cholesterol and control animals. Our opinion is that the only effect of long-lasting hypercholesterolemic diet on the activity of CYP can be caused by hepatic 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 PAR in perfusion medium during the whole perfusion. One should expect that inducers of CYP isoform would cause in the treated animals an increase in metabolite levels compared to the controls while levels of markers are reversely increased in controls and decreased in treated groups. In our case however administration of polyphenolic extract lead to statistically significant increase of both, PAR and 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. Our results suggest, that administration of polyphenolic extract changes the activity of CYP1A2, but on the contrary to the results of other authors, acts as an inductor of CYP1A2 and thus can accelerate activation of specific procarcinogens metabolized by this hepatic isoenzyme. Further investigation should be processed to explain the increased level of PHEN in the 30th minute of perfusion.
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