Induction of cytochrome P450 1A and 213 by (alpha- and beta-ionone in Sprague Dawley rats

Abstract

beta-lonone has been reported to induce the cytochrome P450 (P450) 2131 in rats. In this study, the effects of beta-ionone and an isomer, alpha-ionone, on liver P450 1A and 2B expression in Sprague Dawley rats were investigated. Subcutaneous administration of alpha- and beta-ionone 72 and 48 hr prior to sacrificing the animals induced the liver microsomal P450 1 A and 2B proteins. P450 2B1 induction was associated with the accumulation of its corresponding mRNA. Induction by beta-ionone was much higher than that by alpha-ionone in both the mRNA and protein levels. When the route of administration was compared, P450 2B was induced more strongly after oral administration compared to that after subcutaneous injection. A single oral dose of 100, 300 and 600 mg/kg of alpha- and beta-ionone for 24 h induced P450 2B1-selective pentoxyresorufln O-depentylase activity comparably in a dose-dependent manner. In addition, alpha- and beta-ionone induced the P450 1A and 2B proteins. These results suggest that alpha- and beta-ionone might be potent P450 2B1 inducers in rats, and that both ionones may be useful for examining the role of metabolic activation in chemical-induced toxicity where metabolic activation is required.