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.

Cytochrome P450 mRNA Expression in the Rodent Brain: Species-, Sex-, and Region-Dependent Differences

“…2A). CO has been previously reported to influence P450 expression in the rat liver (Yoo et al, 1990), but it is unclear whether our findings reflect CO-mediated increase in P450 levels in the female mouse hippocampus. Although differences between saline-and CO-treated female mice could be experimental artifact, this seems unlikely because hippocampal expression levels of CYP4X1 and CYP2S1 were comparable between the two vehicle treatments and between sexes.…”

Effect of Dietary Alpha-Linolenic, Eicosapentaenoic and Docosahexaenoic Acids on Liver Microsomal Mixed-Function Oxidases in Rats

“…Yang et al [35] re cently observed that dietary fish oil, as com pared with corn oil, increases the activities of liver microsomal xenobiotic metabolizing enzymes, epoxide hydrolase and UDP-glucuronosyltransferase, and the differences in enyzme activities are paralleled by changes in the enzyme amounts. Yoo et al [24,36] also show that dietary com oil upregulates the liver microsomal activities and amounts of multiple cytochromes P-450 compared 319 with a fat-free diet. However, the precise mechanisms by which dietary fatty acids af fect the constitutive and inducible levels of certain cytochromes P-450 remain to be elu cidated.…”

“…However, dietary DHA increased slightly but significantly the uninduced constitutive level of cytochromes P-450 and the activities of aminopyrine Ndemethylase and aniline hydroxylase as compared with the animals given LN, al though the fatty acid composition of liver microsomal lipids was nearly the same with and without PB induction. PB has been shown to induce greatly the specific species of cytochrome P-450, CYP2B1 and CYP2B2, which are not present virtually as the uninduced constitutive cytochrome P-450 species [23][24][25], PB also induces other species of cytochrome P-450, CYP2A1, 2C6, 2C7, 3AI and 3A2, but the degree of induc tion of these species is at most marginal [23][24][25], Accordingly, the dietary LN, EPA and DHA and/or their endogenous metabo lites did not exert a differential function re spectively to the levels of PB-inducible cyto chromes P-450, possibly to CYP2B1 and CYP2B2. And thus, the dietary whole n-3 fatty acids, as observed previously [12,22], exerted the synergistic stimulation to the PB-inducible cytochromes P-450.…”

“…a-linolenic acid (LN), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on liver microsomal MFO activities induced by PB in rats. Moreover, it is reported that the profiles of liver microsomal cyto chrome P-450 species are remarkably different with and without PB induction [23][24][25]. In addition, little study has been carried out to compare the effects of each n-3 fatty acid sepa rately on the noninduced MFO activities.…”

Diets with Beef Tallow Prevent Acute Acetaminophen Hepatotoxicity Compared to Diets with Soybean Oil in a Rat Model

“…Treatment with acute acetaminophen significantly induced cytochrome 2E1 levels in corn oilfed rats (3-fold increase compared to vehicle control), but not in olive oil-and beef tallow-fed rats (unpublished data, Hwang et al). Yoo et al 43) reported that 20% corn oil or linoleic acid equivalent increased in the concentration of cytochrome P-450 2E1 by 2-to 3-fold. Specifically, 18:2 n-6 as well as the highly unsaturated, long chain fatty acids found in the fish oils (EPA and DHA) have all been shown to be important in this respect.…”