PT - JOURNAL ARTICLE AU - R Agarwal AU - Z Y Wang AU - D P Bik AU - H Mukhtar TI - Nordihydroguaiaretic acid, an inhibitor of lipoxygenase, also inhibits cytochrome P-450-mediated monooxygenase activity in rat epidermal and hepatic microsomes. DP - 1991 May 01 TA - Drug Metabolism and Disposition PG - 620--624 VI - 19 IP - 3 4099 - http://dmd.aspetjournals.org/content/19/3/620.short 4100 - http://dmd.aspetjournals.org/content/19/3/620.full SO - Drug Metab Dispos1991 May 01; 19 AB - Nordihydroguaiaretic acid (NDGA), a plant lignan and phenolic antioxidant, is a known lipoxygenase inhibitor. In this study, we investigated the effect of NDGA on rat epidermal and hepatic monooxygenase activity and its interaction with rat hepatic microsomal cytochrome P-450. The addition of NDGA to epidermal microsomes prepared from control and 3-methylcholanthrene (3-MC)-pretreated rats and hepatic microsomal preparations from control, 3-MC-pretreated, and phenobarbital (PB)-pretreated rats resulted in a concentration-dependent inhibition of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase (ERD) activities. The 50% inhibitory dose for NDGA ranged from 4.1 x 10(-5) to 13.1 x 10(-5) M for AHH and ERD activities in these microsomal preparations. The addition of NDGA to hepatic microsomes prepared from PB-pretreated rats resulted in spectral changes characterized by absorbance maxima at 380 nm and minima at 414 nm, typical of type I binding difference spectra. It also showed time- and concentration-dependent inhibition of the binding of carbon monoxide to dithionite or NADPH-reduced cytochrome P-450. We speculate that perhaps hydroxyl groups present in NDGA play an important role in inhibiting the monooxygenase activity and suggest that NDGA may have potential as an antimutagen and/or anticarcinogen. Furthermore, caution must be exercised in elucidating the role of lipoxygenase in metabolic pathways based solely on the criterion of inhibition by NDGA.