Vitamin E status and metabolism in adult and aged aryl hydrocarbon receptor null mice

摘要

The aryl hydrocarbon receptor (AhR) is involved in regulation of mechanisms for detoxification of xenobiotics, as well as vitamin A metabolism. Vitamin E is a fat-soluble nutrient whose metabolism is initialized via the cytochrome P450 system. Thus, AhR absence could alter hepatic regulation of alpha-tocopherol metabolism. To test this hypothesis, we assessed vitamin E status in adult (2-5 m) and old (21-22 m), wild-type and AhR-null mice. Plasma alpha-tocopherol concentrations in AhR-null mice (23 +/- 1.2 mu mol/L, n=19) were lower than those of wild-type mice (3.2 +/- 1.2, n=17, P=.0131); those in old mice (3.2 1.2, n=20) were higher than those of adults (2.2 +/- 1.0, n=16, P=.0075). Hepatic alpha-tocopherol concentrations were not different between genotypes, but were nearly double in old (32 8 nmol/g, n=20) as compared with adult mice (17,12, n=16, P<.0001). Hepatic Cyp3a concentrations in AhR-null mice were greater than those in wild-type mice (P=.0011). Genotype (P=.0047), sex (P<.0001) and age (P<.0001) were significant modifiers of liver alpha-tocopherol metabolite (alpha-CEHC) concentrations. In general, Cyp3a concentrations correlated with hepatic alpha-tocopherol (r=0.3957, P<.05) and alpha-CEHC (r=0.4260, P<.05) concentrations. Since there were rio significant genotype differences in the hepatic alpha- or gamma-tocopherol concentrations, AhR-null mice did not have dramatically altered vitamin E metabolism. Since they did have higher hepatic alpha-CEHC concentrations, these data suggest metabolism was up-regulated in the AhR-null mice in order to maintain the hepatic tocopherol concentrations similar to those of wild-type mice