lignans and 2-7-8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman

The mechanisms underlying the preferential retention of a single compound (α-tocopherol (αT)) of the eight vitamin E compounds in the body are incompletely understood. We hypothesized that vitamin E metabolism and not the hepatic α-tocopherol transfer protein (TTP) is responsible for the discrimination against non-αT congeners.. TTP knockout and wild-type mice (n = 12/group) were fed equimolar concentrations of αT and γ-tocopherol (γT; 50 mg/kg diet each) alone or together with sesamin (2 g/kg diet) for 6 wk. Inhibition of vitamin E metabolism with sesamin, but not TTP knockout, increased γT tissue concentrations. TTP-expressing and TTP-free cells were incubated with equimolar concentrations of αT and γT (25 μmol/L each) with or without sesamin (2 μmol/L). The preferential degradation of γT independently of TTP expression was confirmed and a decrease in the production of the metabolite γ-carboxyethyl hydroxychromanol (CEHC) with increasing TTP expression revealed. Displacing γT from TTP in these cells by incubation with increasing αT concentrations enhanced the secretion of γ-CEHC in TTP-transfected cells, suggesting that TTP might protect γT from β-oxidation.. We conclude that vitamin E metabolism and not TTP controls γT concentrations in vivo and observed an interaction of TTP with vitamin E metabolism that results in reduced production of the metabolite γ-CEHC.

Topics: alpha-Tocopherol; Animals; Carrier Proteins; Chromans; Dioxoles; Female; gamma-Tocopherol; Hep G2 Cells; Humans; Lignans; Liver; Mice; Mice, Knockout; Mixed Function Oxygenases; Oxidation-Reduction; Propionates

We showed previously that dietary sesame seed and its lignans elevate the tocopherol concentration in rats. To clarify their effect on tocopherol metabolism, we determined in this study the urinary excretion of 2,7,8-trimethyl-2(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC), a gamma-tocopherol metabolite, in rats fed sesame seed or its lignans. Rats were fed diets with or without sesame seed for 28 d in Experiment 1, and for 1, 3 and 7 d in Experiment 2. On d 28, dietary sesame seed elevated (P < 0.05) gamma-tocopherol concentrations in liver, kidney, brain and serum, and decreased (P < 0.05) urinary excretion of gamma-CEHC. The excretion was completely inhibited by feeding sesame seed on d 1 and 3. In Experiment 3, the effects of dietary sesamin and sesaminol (major lignans in sesame seed) or ketoconazole (a selective inhibitor of cytochrome P(450) (CYP)3A on urinary excretion of gamma-CEHC in rats fed gamma-tocopherol were examined. The urinary gamma-CEHC in rats fed sesamin or sesaminol was markedly lower than in rats fed gamma-tocopherol alone (P < 0.05). Dietary ketoconazole also inhibited (P < 0.05) urinary excretion of gamma-CEHC, and elevated (P < 0.05) gamma-tocopherol concentrations in tissues and serum of rats fed gamma-tocopherol. These data suggest that sesame seed and its lignans elevate gamma-tocopherol concentration due to the inhibition of CYP3A-dependent metabolism of gamma-tocopherol.

Topics: Animals; Antioxidants; Aryl Hydrocarbon Hydroxylases; Brain; Chromans; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; gamma-Tocopherol; Kidney; Lignans; Liver; Male; Oxidoreductases, N-Demethylating; Pedaliaceae; Propionates; Rats; Rats, Wistar; Seeds; Sesame Oil; Time Factors