The effect of the tert-butylquinone metabolite of butylated hydroxyanisole on cytochrome P-450 monooxygenase activity.

S W Cummings, B B Curtis, J A Peterson, R A Prough

Index: Xenobiotica 20(9) , 915-24, (1990)

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Abstract

1. The t-butylquinone metabolite of BHA was shown to redox cycle with NADPH-cytochrome P-450 reductase leading to enhanced NADPH-oxidase activity for both the purified and liver microsome-bound flavoprotein. Likewise, addition of t-butylquinone (20-100 microM) strikingly inhibited electron transfer from the flavoprotein reductase to cytochrome P-450 of liver microsomes from phenobarbital-treated rats. 2. When the effect of t-butylquinone on metabolism of biphenyl was evaluated with liver microsomal fractions or isolated hepatocytes, t-butylquinone was less effective as an inhibitor then BHA alone or vitamin K3 (menadione). Addition of dicoumarol had little or no effect on the inhibitory potency of either t-butylquinone or vitamin K3 in isolated hepatocytes. 3. t-Butylquinone was not an effective reductant for exogenous oxidants, such as cytochrome c, in the presence of purified, cytosolic NAD(P)H-quinone oxidoreductase (DT-diaphorase). This property is most probably due to the lower rate of reoxidation of t-butylquinone by molecular oxygen, relative to vitamin K3 (menadione).