Inhibition of cytochrome P-450 activity in rat liver microsomes by the naturally occurring flavonoid, quercetin

摘要: Abstract The kinetic characteristics and mechanism of flavonoid inhibition cytochrome P-450-mediated reactions were examined in rat liver microsomes, using the naturally occurring flavonoid, quercetin (3,3′,4′,5,7-pentahydroxyflavone). Quercetin inhibited O-deethylation ethoxyresorufin β-naphthoflavone-induced microsomes by 15–80% at concentrations 10–250 n m . pattern was dependent on concentration. also p-nitroanisole demethylation benzo(a)pyrene hydroxylation, but did not change proportions individual metabolites comparison to controls. Specific steps P-450 reaction pathway tested for sensitivity inhibition. Km values substrates increased presence quercetin; competition and/or alteration substrate binding site contributes In experiments under anaerobic, carbon monoxide-saturated conditions, inhibit reduction NADPH-cytochrome reductase. cumene hydroperoxide-supported (15–60% 50–300 ), suggesting that may interfere with formation or breakdown oxygenated heme complex. Stoichiometry established is a potent uncoupler reactions, elevating rates H2O2 almost twofold. Structure/activity studies indicated certain other flavonoids least as inhibitors deethylation quercetin. These findings are interest light significant dietary exposure human population flavonoids.