Vitamin E status and metabolism in adult and aged aryl hydrocarbon receptor null mice.
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 α-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 α-tocopherol concentrations in AhR-null mice (2.3±1.2 μmol/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 α-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±2, 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 α-tocopherol metabolite (α-CEHC) concentrations. In general, Cyp3a concentrations correlated with hepatic α-tocopherol (r=0.3957, P<.05) and α-CEHC (r=0.4260, P<.05) concentrations. Since there were no significant genotype differences in the hepatic α- or γ-tocopherol concentrations, AhR-null mice did not have dramatically altered vitamin E metabolism. Since they did have higher hepatic α-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.
Traber
Maret G
MG
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-6512, USA. maret.traber@oregonstate.edu
Mustacich
Debbie J
DJ
Sullivan
Laura C
LC
Leonard
Scott W
SW
Ahern-Rindell
Amelia
A
Kerkvliet
Nancy
N
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002839:Chromans / Q000032:analysis / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism; D024502:alpha-Tocopherol / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D024504:gamma-Tocopherol / Q000032:analysis / Q000097:blood / Q000378:metabolism*
D000975:Antioxidants; D051792:Basic Helix-Loop-Helix Proteins; D002839:Chromans; D003577:Cytochrome P-450 Enzyme System; D018336:Receptors, Aryl Hydrocarbon; D015262:Xenobiotics; D024502:alpha-Tocopherol; D024504:gamma-Tocopherol; C484722:Ahr protein, mouse; C483420:carboxyethyl-hydroxychroman