HETEROGENOUS EFFECTS OF NATURAL FLAVONOIDS ON MONOOXYGENASE ACTIVITIES IN HUMAN AND RAT-LIVER MICROSOMES

The in vitro effects of nine flavonoids on different monooxygenase act ivities from human and rat liver were investigated. Flavonoids belongi ng to different chemical classes [flavones (chrysin, tangeretin, flavo ne, 5,6-benzoflavone, 7,8-benzoflavone), flavonols (quercetin), and fl avanones (pinocembrin, eriodictyol, flavanone)] were chosen. Ethoxyres orufin O-deethylase (EROD) and benzyloxyresorufin O-debenzylase (BROD) were selected as marker activities of P450 isoenzymes involved in car cinogen activation. Human EROD activity was inhibited by all flavonoid s. Flavonoids without hydroxyl groups were more effective than those w ith hydroxyl groups. Flavonoids with an unsaturated flavane nucleus we re more inhibitory than the corresponding saturated analogues. Similar structure-activity relationships were found in microsomes from methyl cholanthrene-treated rats. The effects of flavonoids on human BROD act ivity were quite different from those observed on EROD activity. Nonhy droxylated flavones were effective activators. Hydroxylated flavonoids showed a biphasic effect, being activators at low concentrations and inhibitors at higher concentrations. The effects of flavonoids on BROD activity were rather similar in man and control rats. (C) 1995 Academ ic Press, Inc.