Cytochrome P4503A-Dependent Metabolism of Tocopherols and Inhibition by Sesamin

Sontag, Timothy J.; Swanson, Joy E.

doi:10.1006/bbrc.2000.3706

Cited by 195 publications

(149 citation statements)

References 21 publications

Supporting

Mentioning

139

Contrasting

Unclassified

Order By: Relevance

“…It has been reported that the intake of sesame seeds and sesame lignan can cause a marked increase of the a-tocopherol concentration in the blood and tissues of rats (Yamashita et al, 1995), and that sesamin inhibits the metabolism of tocopherol to CEHC by HepG2=C3A cells (Parker et al, 2000). Parker also studied the metabolism of tocopherol to CEHC by cultured cells and the inhibition of its metabolism by ketoconozole, and suggested that cytochrome P4503A might be involved in vitamin E metabolism (Parker et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Measurement of vitamin E metabolites by high-performance liquid chromatography during high-dose administration of α-tocopherol

et al. 2003

View full text Add to dashboard Cite

Method: a-Tocopherol and g-tocopherol are metabolized into 2,5,7,8-tetramethyl-2-(2 0 -carboxyethyl)-6-hydroxychroman (a-CEHC) and 2,7,8-trimethyl-2-(2 0 -carboxyethyl)-6-hydroxychroman (g-CEHC), respectively. We analyzed a-and g-CEHC concentrations in human serum and urine by high-performance liquid chromatography during administration of a-tocopherol. Fourteen healthy adult male volunteers received 1200 IU per day of RRR-a-tocopherol for 28 days. Blood and urine samples were obtained on days 0, 14, 28, and 56. Results: During a-tocopherol administration, the plasma g-tocopherol concentration decreased significantly, but there was marked elevation of the a-tocopherol concentration. Increased concentration of a-CEHC and g-CEHC in both serum and urine indicated the acceleration of vitamin E metabolism. Conclusion: High-dose administration of a-tocopherol caused an increase of g-tocopherol metabolism, which might have caused a decrease of the plasma g-tocopherol concentration.

show abstract

Section: Discussionmentioning

confidence: 99%

Measurement of vitamin E metabolites by high-performance liquid chromatography during high-dose administration of α-tocopherol

et al. 2003

View full text Add to dashboard Cite

show abstract

“…In contrast, in wild-type fetuses, low-dose VE consistently failed to increase a-tocopherol levels in any tissue, which accounts for the absence of any reduction in oxidative DNA damage in þ/þ p53 fetuses. The mechanisms underlying this differential VE disposition in wild-type fetuses are not clear; but, as for the tissue-selective differences, these may include variations in membrane transporters 37,38 and, at least in the liver, metabolism of a-tocopherol by the cytochromes P450 CYP3A4 and CYP4F2, 39,40 which may be expressed the fetus towards the end of gestation. 41,42 The tissue-and p53 genotype-dependent nature of the antioxidative efficacy of low-dose VE may explain, in part, the conflicting published reports of antitumor efficacy of VE for different cancers.…”

Section: In Utero Origins Of Cancer/chen Et Almentioning

confidence: 99%

Reduced tumorigenesis in p53 knockout mice exposed in utero to low‐dose vitamin E

Chen

Squire

Wells

2009

Cancer

View full text Add to dashboard Cite

BACKGROUND: The limited antioxidative capacity of the fetus renders it more susceptible to reactive oxygen species (ROS), and possibly to ROS‐mediated cancer initiation or promotion in utero. METHODS: To test this hypothesis, pregnant cancer‐prone p53 knockout mice were prenatally supplemented with a low dietary dose of the antioxidant vitamin E (VE) (0.1% all‐rac‐α‐tocopherol‐acetate), and the homozygous (−/−) and heterozygous (+/‐) p53‐deficient and wild‐type (+/+) offspring were examined for VE levels, oxidative DNA damage, chromosomal stability, cellular viability and postnatal tumorigenesis. RESULTS: In utero exposure to VE reduced spontaneous postnatal tumorigenesis in p53 +/‐ offspring, and increased VE levels and reduced fetal DNA oxidation in some but not all tissues of p53‐deficient fetuses. Survival of VE‐exposed p53 +/‐ offspring at the end of the study was double that of the +/‐ controls (45% vs 23%). In primary culture of skin fibroblasts from VE‐exposed fetuses, VE did not alter chromosomal ploidy, but reduced cell death, indicating that its protective effect did not involve chromosomal stability. CONCLUSIONS: The tissue‐selective increase in fetal VE levels and reduced DNA oxidation, together with a concomitant reduction in postnatal tumorigenesis, suggest that in utero oxidative stress contributes to some postnatal cancers, and the risk can be reduced by maternal dietary supplementation with low‐dose VE. Cancer 2009. © 2009 American Cancer Society.

show abstract

“…CYP3A has ω-hydroxylase activity and was first reported to be involved in vitamin E metabolism because of changes in levels of CEHC metabolites in HepG2 cells when a CYP inhibitor, ketoconazole (KCZ), or a CYP inducer, rifampicin, was added to the medium [12,13]. In the present study, despite a significant induction of CYP3A protein in both OFO-treated groups, the excretion of α-CEHC in the urine was not significantly increased in the OFE group compared to the CO group.…”

Section: Discussionmentioning

confidence: 99%

“…First, levels of the metabolite product of α-tocopherol in the urine, α-carboxyethyl hydroxychroman (α-CEHC) [11], might be increased if α-tocopherol catabolism in liver were enhanced. α-CEHC is reported to be produced by cytochrome P450 3A (CYP3A), the xenobiotic metabolizing enzyme [12,13]. Second, since α-tocopherol can be excreted in the feces with bile [14], the higher levels of radiolabeled α-tocopherol in the feces could come from increased bile excretion.…”

Section: Introductionmentioning

confidence: 99%

Effects of Oxidized Frying Oil on Proteins Related to α-Tocopherol Metabolism in Rat Liver

Huang

Kang

et al. 2009

J. Clin. Biochem. Nutr.

View full text Add to dashboard Cite

Summary An oxidized frying oil (OFO) diet has been reported to induce an increase in lipid peroxidation and a reduction in vitamin E status in animal tissues. This study was performed to investigate how vitamin E metabolism is influenced by OFO. Male Wistar rats were divided into three groups, a control group (CO) and two OFO-fed groups (OF and OFE). The diet of the OFE group was supplemented with an extra 50 mg/kg of α-tocopherol acetate and thus contained twice as much vitamin E as that of the OF group. After six weeks on these diets, liver α-tocopherol levels in the OF group were the significantly lowest among the three groups. Excretion of the α-tocopherol metabolite, α-carboxyethyl hydroxychroman (α-CEHC) in the urine was significantly lower in the OF group than in the other two groups. There were no significant differences in protein levels of α-tocopherol transfer protein (α-TTP) and multidrug resistance protein among the three groups. Protein levels of cytochrome P450 monooxygenase (CYP) 3A, CYP4A, and catalase were markedly increased in both groups on the OFO diet. This suggests that an OFO diet may interfere with medicine metabolism and needs further investigation.

show abstract

Cytochrome P4503A-Dependent Metabolism of Tocopherols and Inhibition by Sesamin

Cited by 195 publications

References 21 publications

Measurement of vitamin E metabolites by high-performance liquid chromatography during high-dose administration of α-tocopherol

Measurement of vitamin E metabolites by high-performance liquid chromatography during high-dose administration of α-tocopherol

Reduced tumorigenesis in p53 knockout mice exposed in utero to low‐dose vitamin E

Effects of Oxidized Frying Oil on Proteins Related to α-Tocopherol Metabolism in Rat Liver

Contact Info

Product

Resources

About