EVIDENCE FOR TANGERETIN O-DEMETHYLATION BY RAT AND HUMAN LIVER-MICROSOMES

1. Tangeretin, a polymethoxylated flavone, was studied as a substrate for cytochrome P450-catalysed demethylation reactions by rat and human liver microsomes. Evidence has been presented for the production of f ormaldehyde in the presence of tangeretin and NAD(P)H. Kinetic studies showed a K(m) value for tangeretin of about 18 muM in both species. 2 . The reaction was inhibited by CO, piperonyl butoxide, 7,8-benzoflavo ne, propyl gallate, aminobenzothiazole and metyrapone. 3. Rats pretrea ted with classical cytochrome P450 inducers (Aroclor 1254, 3-methylcho lanthrene, phenobarbital, dexamethasone and ciprofibrate) or with flav onoids (flavone, flavanone, quercetin and tangeretin) resulted in incr eased microsomal demethylation of tangeretin after 3-methylcholanthren e and flavone only. Tangeretin did not enhance its own metabolism. 4. Tangeretin interacted with the oxidized form of cytochrome P450 to pro duce a reverse type I spectrum. 5. Results indicate that tangeretin is metabolized in liver microsomes by an O-demethylation reaction involv ing cytochrome P450.