COMPARATIVE EFFECTS OF FLAVONOIDS AND MODEL INDUCERS ON DRUG-METABOLIZING-ENZYMES IN RAT-LIVER

The inducing effects of some flavonoids (flavone, flavanone, tangereti n and quercetin) and model substances have been studied in rats, and t he activity and the expression of drug-metabolizing enzymes have been compared in rats. The addition of flavonoids to the diet (0.3% w/w) fo r 2 weeks did not change the liver cytochrome P450 content nor the act ivities of the NADPH-cytochrome P450 and NADH-cytochrome b(5) reductas es, but it affected the activities of phase I and phase II enzymes. Fl avone, and to a lesser extent tangeretin, increased the activities med iated by the P450 1A1,2 (EROD) and 2B1,2 (PROD) as well as the activit ies of p-nitrophenol UDP-glucuronyl transferase (UGT) and glutathione transferase (GST). Flavanone mainly enhanced PROD, UGT and GST, wherea s quercetin did not modify any enzyme activities. None of the tested f lavonoids modulated the activities catalyzed by P450 2E1, 3A and 4A. I mmunoblotting studies showed that flavone and tangeretin increased the expression of cytochrome P450 1A and 2B forms, whereas flavanone only induced cytochrome P450 2B. Flavone and to a lesser extent flavanone, markedly increased the phenol-UGT protein level. Both flavone and fla vanone also increased the androsterone- and testosterone-UGTs, whereas tangeretin and quercetin did not increase any UGT isoform. We conclud ed that the flavonoids tested specifically affected the expression of the drug-metabolizing isozymes in rat liver, their inducing properties were dependent on their chemical structures.