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METABOLISM OF 3, 7-DIHYDROXYFLAVONE MEDIATED BY CYTOCHROME P450

Flavonoids are a large group of compounds, that people consume from fruits and vegetables. iological effects of these xenobiotics have been extensively studied in vitro. As human body has been exposed to flavonoids through food, ourorganism has developed mechanism to prevent absorption or stimulate excretions e.g. transporters and metabolism.Although results of in vitro studies are promising due to low bioavailability these compounds do not demonstrate theirpharmacological potential in vivo. Thus, the objective of this work was to characterize metabolism mediated bycytochromes P450 of 3, 7-dihydroxyflavone, flavonoid studied for its anticancer properties. For this purpose, human livermicrosomes and recombinant cytochrome P450 enzymes were used. Metabolism was monitored by liquidchromatography coupled with mass spectrometry (electron spray ionization, time of flight detection) for metabolitedetermination and diode array detector for quantification. Major metabolic reaction was hydroxylation generating 3, 7, 4'‐trihydroxyflavone as a predominant product. Based on screening on human liver microsomes with specific inhibitors ofcytochromes P450, major enzyme mediating metabolism of 3, 7-dihydroxyflavone was shown to be CYP1A2. Catalyticefficiency of 0.012±0.005 x 10-6 min-1M-1 was determined on human liver microsomes. These data will improveunderstanding of pharmacokinetics of flavonoids, helping overcome low bioavailability observed in vivo.

cytochrome P450, flavonoids

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