Effects of Perilla frutescens Extract on Cytochrome P450 Expression in Oxidative Stress‐induced Liver

Abstract

We have previously reported protective effect of Perilla frutescens extract (PLE) against tert‐butyl hydroperoxide (t‐BHP)‐induced liver oxidative damage in rats. t‐BHP induces lipid peroxidation in rat liver microsomes and it is reported that t‐BHP can be metabolized to free radical intermediates by cytochrome P450 (CYP), which can subsequently initiate lipid peroxidation. We speculate that lipid peroxidation in rat liver microsomes was induced by t‐BHP is closely linked with the oxidative metabolism mediated by CYP1A1/2 and CYP 3A/2E1. We examined the effect of the PLE on CYP activities including Ethoxyresorufin‐O‐deethylase (EROD, CYP1A1), Methoxyresorufin‐O‐deethylase (MROD, CYP1A2), Erythromycin‐N‐demethylase (ERDM, CYP3A) and p‐nitrophenol hydroxylase (PNPH, CYP2E1) under oxidative stress in rat liver. The pretreatment of rats with PLE (250, 500 and 1000 mg/kg b.w.) for 5 days before a single dose of t‐BHP (i.p.; 0.5 mmol/kg), PLE was found to be a potent inhibitory effect CYP 1A1/2 of oxidative stress‐induced liver microsomes. Kinetic analysis of CYP 1A1/2 activity of t‐BHP‐induced microsomes demonstrated that PLE inhibited enzyme activities by competitive or noncompetitive mechanism. These data suggest that selective control of CYP by PLE might contribute to protective effect of liver through inhibitory CYP activities against oxidative stress in rat liver.