Specificity of medicarpin and related isoflavonoids in inhibition of rat hepatic mixed function oxidase activity.

The cytochromes P-450 of the mixed function oxidase system metabolize a wide variety of endogenous compounds to either nontoxic products or toxic metabolites. A number of natural products, such as flavonoids, influence this metabolism. Exposure to these compounds may therefore be a factor in animal and human responsiveness to cytochrome P-450 substrates. We have examined the effect of the pterocarpan medicarpin on the cytochrome P-450-dependent aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin deethylase (ECD) activities of rat liver microsomes. Medicarpin and maackiain and two of their biosynthetic precursors inhibit the constitutive and phenobarbital (PB)-induced types of AHH, but have little effect on the 3-methylcholanthrene (MC)-induced type of AHH. This is in contrast to the effect of the commonly used cytochrome P-450 inhibitor 7,8-benzoflavone, which inhibits the hepatic AHH of MC-treated rats and has no effects on the AHH of control or PB-treated rats. However, medicarpin inhibited the constitutive as well as the PB- and MC-induced ECD. The specific modulatory effect as well as its relative availability suggests the utility of medicarpin as a probe for different forms of cytochrome P-450 in animal tissues.