Roles of dietary corn oil in the regulation of cytochromes P450 and glutathione S-transferases in rat liver

Abstract

To study the molecular mechanisms by which dietary lipids affect the levels of cytochrome P450 (P450) isozymes, male Sprague-Dawley rats were fed either fat-free (FF) or 20% corn oil (CO) diet in combination with one of the following three treatments: no inducer, phenobarbital (PB) and acetone. Dietary CO did not affect the constitutive level of P450IIB (PB-inducible), but it affected the induction of P450IIB by PB treatment. The induction of P450IIB by PB in the CO group as determined by 7-pentoxy-resorufin O-dealkylase activity and immunochemically detected protein level was twofold higher than that in the FF group, and this difference was also reflected in the level of mRNA for this enzyme. In contrast, dietary CO increased the constitutive level of P450IIE (ethanol-inducible) twofold as indicated by N-nitrosodimethylamine demethylase activity and immunochemically detectable protein, but it had no effect on the induction of P450IIE by acetone. The induced level of P450IIE by acetone in the CO group did not differ from that in the FF group as measured by the enzyme activity and protein level. It was demonstrated that dietary CO affects P450IIB and IIE activities by altering the concentration of the isozymes rather than by modulating their catalytic activities. In addition, dietary CO increased the microsomal testosterone 6 beta-hydroxylase activity but not 7 alpha- and 2 alpha-hydroxylase activities, suggesting an increase in P450IIIA and/or IIC13 but not in IIA1 and IIC11, respectively. Dietary CO also affected the constitutive and induced levels of glutathione S-transferase (GST) isozymes in a different manner: it increased the constitutive level of GST-B but not that of GST-A. Nevertheless, it was important for the induction of both GST-A and GST-B by PB treatment. The results suggest that lipid nutrition affects xenobiotic metabolism activities by altering constitutive and inducible levels of certain P450 and GST isozymes.