METABOLISM OF ALPHA-NAPHTHOFLAVONE BY RAT-LIVER MICROSOMES

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  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (7) , 2621-2626
Abstract
.alpha.-Naphthoflavone (ANF) or 7,8-benzoflavone, a synthetic flavanoid, inhibits benzo(a)pyrene metabolism by .beta.-naphthoflavone (BNF)-induced rat liver microsomes, but has no inhibitory effects on benzo(a)pyrene metabolism in phenobarbital (PB)-induced rat liver microsomes. ANF gives type 1 binding spectra with BNF- and PB-induced rat liver microsomes and is metabolized by both. Specific metabolites identified by UV and mass spectra and in some cases, by cochromatography with authentic standards were 6-hydroxy-.alpha.-naphthoflavone, 9-hydroxy-.alpha.-naphthoflavone, .alpha.-naphthoflavone-5,6-oxide and 5,6-dihydro-5,6-dihydroxy-.alpha.-naphthoflavone. Metabolism at the 5,6 bond of ANF accounted for 73 and 86% of the total organic soluble metabolites produced by PB- and BNF-induced microsomes, respectively. This result is in concert with previous observations on the role of 6 substitution and the loss of inhibitory activity of ANF in BNF-induced rat liver microsomes. Metabolism of ANF is mediated by the cytochrome P-450 mixed-function oxidase because it is dependent on NADPH and is inhibited by carbon monoxide and other cytochrome P-450 inhibitors. BNF-induced microsomes metabolize ANF to 5,6-dihydro-5,6-dihydroxy-.alpha.-naphthoflavone to a much greater extent than do PB-induced microsomes.