engleski

INACTIVATION KINETICS OF CYTOCHROME P450 3A4 BY ACACETIN

Flavonoids are secondary plant metabolites found in fruits and vegetables. Cytochrome P450 enzymes are the most significant metabolic enzymes of xenobiotics, including food constituents, toxic substances, medications. Some flavonoids can interact with other drugs by inhibiting cytochrome P450 enzymes. The objective of this study was to determine inhibition kinetics of cytochrome P450 3A4 by acacetin. Acacetin is one of the major polyphenols present in honey, which is believed to be associated with the prevention of heart disease. Enzyme activity was determined using testosterone and nifedipine as marker substrates, and generation of respective metabolites 6β-hydroxytestosterone and nifedipine-oxide was monitored by high performance liquid chromatography coupled with diode array detector. In testosterone assay the values of inactivation kinetic parameters were as follows: IC50 value of 10.9 ± 0.3 µM, inhibition constant 6 ± 3 µM, inhibition rate constant 0.036 ± 0.006 per min Similar results were obtained in nifedipine assay. Further in vitro studies are needed to determine the reactive intermediate responsible for inactivation of cytochrome P450 3A4 enzyme, as well as in vivo studies to determine possible clinical significance of this inhibition.

flavonoids, cytochrome P450 3A4, inhibition, kinetics, acacetin

nije evidentirano