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-Tocopherol1
Department of Food and Nutrition, School of Life Studies, Sugiyama Jogakuen University, Nagoya 464-8662, Japan
2To whom correspondence should be addressed. E-mail: kanaey{at}food.sugiyama-u.ac.jp.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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-CEHC), a -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) -tocopherol concentrations in liver, kidney, brain and serum, and decreased (P < 0.05) urinary excretion of -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 P450 (CYP)3A on urinary excretion of -CEHC in rats fed -tocopherol were examined. The urinary -CEHC in rats fed sesamin or sesaminol was markedly lower than in rats fed -tocopherol alone (P < 0.05). Dietary ketoconazole also inhibited (P < 0.05) urinary excretion of -CEHC, and elevated (P < 0.05) -tocopherol concentrations in tissues and serum of rats fed -tocopherol. These data suggest that sesame seed and its lignans elevate -tocopherol concentration due to the inhibition of CYP3A-dependent metabolism of -tocopherol.
KEY WORDS: • carboxychroman • cytochrome P450 • rats • sesame lignan • sesame seed • -tocopherol
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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-, ß-, - or 
-tocopherols and -, ß-, - or -tocotrienols; among these isoforms, -tocopherol shows the highest biological activity. Duthie et al. (1
) and Saldeen et al. (2
) have reported that the antioxidative effect of -tocopherol on lipid peroxidation in vitro is more potent than that of -tocopherol. Moreover, Cooney et al. (3
) and Christen et al. (4
) showed that -tocopherol trapped reactive nitrogen oxide species generated during inflammation in vitro. However, the antioxidative activity of -tocopherol in vitro is poorly correlated with its biological activity. Bieri and Evarts (5
) reported that the relative bioactivity of -tocopherol is 
10% of that of -tocopherol.
Dietary vitamin E isoforms are absorbed in the intestine and carried to the liver as a result of the uptake of chylomicron remnants (6
). There is no discrimination between -tocopherol and other isoforms during absorption and chylomicron secretion by the intestine (7
,8
). -Tocopherol transfer protein (-TTP)3
catalyzes -tocopherol secretion by a novel non-Golgi–mediated pathway in liver cells, and -tocopherol is incorporated into VLDL and transported to the various tissues by lipoproteins (9
). The other isoforms of vitamin E such as -tocopherol are excreted because their affinity for -TTP is low. Therefore, the -tocopherol concentrations in tissues and blood are greater than those of other isoforms in humans (10
) and rats (11
,12
). Hosomi et al. (13
) reported that the relative affinity of tocopherol isoforms or -tocotrienol for -TTP correlates well with their biological activities. Thus, the affinity of vitamin E isoforms for -TTP is a critical determinant of their biological activities, and the low biological activity of -tocopherol may be due to its low affinity for -TTP.
However, we showed previously that dietary sesame seed and its lignans markedly elevate -tocopherol concentrations in the liver, kidney and plasma of rats fed a diet without -tocopherol (14
). Recently, Lemcke-Norojärvi et al. (15
) reported that dietary sesame oil elevated the -tocopherol concentration in the serum of Swedish women. Sesame seed is rich in -tocopherol, but contains negligible amounts of -tocopherol. We also showed that dietary sesame seed elevates the -tocopherol concentrations in the liver, kidney and plasma of rats fed a diet with -tocopherol (16
), and the - and -tocotrienol concentrations in the adipose tissue and skin of rats fed a tocotrienol-rich fraction extracted from palm oil (12
). These results indicate that sesame seed and its lignans affect vitamin E metabolism. The precise mechanism of the elevation of vitamin E concentrations by sesame lignans is unknown. Dietary sesame seed does not inhibit -tocopherol secretion into bile (17
). Recently, many reports have indicated that tocopherols and tocotrienols are metabolized to carboxychromans and excreted into urine in humans (18
–20
) and rats (21
,22
). Parker et al. (23
) recently reported that the oxidative catabolism of tocopherol to carboxychroman is catalyzed by cytochrome P450 (CYP)3A in HepG2 cells, a well-differentiated human hepatoblastoma line derived from a hepatocellular carcinoma. Birringer et al. (24
) also showed that a CYP3A-type cytochrome initiates -tocopherol metabolism by 
-oxidation, the rate-limiting step in tocopherol metabolism, in HepG2 cells. Moreover, Parker et al. (23
) reported that sesamin, a major sesame lignan, strongly inhibits carboxychroman production in HepG2 cells. These results suggest that the inhibition of the CYP3A-dependent metabolism of tocopherols in the liver by dietary sesame lignans causes the elevation of tocopherol concentrations in rats. Therefore, we determined the urinary excretion of 2,7,8-trimethyl-2(2'-carboxymethyl)-6-hydroxycroman (-CEHC), a metabolite of -tocopherol, in rats fed sesame seed with the aim of clarifying the effect of dietary sesame lignans on the tocopherol metabolism in vivo. Here we show the inhibition of the urinary excretion of -CEHC by feeding sesame seed over long (28 d) and short (1, 3 and 7 d) periods. The data further suggest that sesame lignan is a potent inhibitor of CYP3A, which is involved in tocopherol metabolism in vivo.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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-CEHC used as standard, along with - and -tocopherols, was generously donated by Eisai (Tokyo, Japan). Roasted white sesame seed was a gift of Shinsei (Aichi, Japan). Sesamin and sesaminol were donated by Takemoto Oil & Fat (Aichi, Japan). Ketoconazole was purchased from Biomol Research Laboratories (Plymouth Meeting, PA).
Male Wistar rats (3 wk old) were purchased from Japan SLC (Shizuoka, Japan). They were maintained at 24.5°C with a 12-h light cycle (lights on from 0800 to 2000h) and allowed free access to water and food. The rats were fed a commercial diet (CE-2, Clea Japan, Tokyo, Japan) for 7 d before the start of each experiment. The composition of the experimental diet is shown in Table 1
. The rats were killed between 1000 and 1300 h, and all procedures were performed in accordance with the Animal Experimentation Guidelines of Nagoya University.
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The rats were fed a diet without vitamin E (the deficient group, n = 6), a diet containing 50 mg -tocopherol/kg (the -Toc group, n = 6) or a diet containing 200 g sesame seed/kg (the sesame group, n = 6) for 28 d; 200 g of sesame seed contains 50 mg of -tocopherol and negligible amounts of -tocopherol. After 24 h of food deprivation, the rats were killed by decapitation, and liver, kidney, brain and serum were taken and stored at -80°C until use for the determination of tocopherol and thiobarbituric acid reactive substance (TBARS) concentrations. Urine was collected in a test tube, kept cool with dry ice for the last 12 h, and lyophilized and stored at -80°C under nitrogen until used for the determination of -CEHC concentration.
Rats were fed a diet without vitamin E for 28 d, and then a diet without vitamin E (the deficient group, n = 6), a diet containing 50 mg -tocopherol/kg (the -Toc group, n = 6) or a diet containing 200 g sesame seed/kg (the sesame group, n = 6) for 1, 3 and 7 d. The rats were not deprived of food, and urine was collected into a test tube for the last 24 h. Tissues, serum and urine were sampled and handled as described for Experiment 1.
Rats were fed the diet without vitamin E for 28 d, and then the diet without vitamin E (the deficient group, n = 6) for 3 d, the diet containing 50 mg -tocopherol/kg (the -Toc group, n = 6), the diet containing 200 g sesame seed/kg (the sesame group, n = 6), the diet containing 50 mg -tocopherol/kg and 2 g sesamin/kg (the -Toc + sesamin group, n = 6), the diet containing 50 mg -tocopherol/kg and 2 g sesaminol/kg (the -Toc + sesaminol group, n = 6) or the diet containing 50 mg -tocopherol/kg and 1 g ketoconazole/kg (the -Toc + keto group, n = 6). The rats were not deprived of food and urine was collected for the last 24 h. Tissues, serum and urine were sampled and handled as described for Experiment 2.
- and -tocopherol concentrations.">Determination of - and -tocopherol concentrations.
Tocopherols in the tissues and serum were extracted as described previously (17
). Concentrations of - and -tocopherol were determined by HPLC (26
). Instrumentation used for HPLC was a Shimadzu LC-10AS (Shimadzu, Kyoto, Japan) with a Shimadzu RF-10AXL fluorescence detector (excitation 298 nm, emission 325 nm). The analytical column used was a Develosil NH2-5 (4.6 x 150 mm, Nomura Chemical, Aichi, Japan). The mobile phase was hexane containing 1%(v/v) isopropylalcohol, and the flow rate was 1 mL/min.
-CEHC.">Determination of urinary amount of -CEHC.
Both conjugated and unconjugated -CEHC in the urine were methylated and extracted by the method of Kiyose et al. (21
), and the concentration was determined using HPLC with an electrochemical detector.
Water (60 mL) was added to lyophilized urine collected for 24 h, and 0.5 mL of the urine sample was added to 0.1 mL of 500 g/L ascorbic acid and 1 mL of 0.54 mmol/L EDTA. The urine sample was methylated in 3 mol/L methanolic hydrochloric acid at 60°C for 1 h under nitrogen, and the methylated tocopherol metabolite was extracted with hexane. The hexane was evaporated by nitrogen, and the residue was dissolved in 100 µL of 45% (v/v) acetonitrile containing 50 mmol/L sodium perchlorate; 10 µL of this solution was subjected to HPLC.
Instrumentation used for HPLC was a Shimadzu LC-10AS with a Coulochem II electrochemical detector (MC Medical, Osaka, Japan) and an ODS-3 column (250 x 2.1 mm, GL Science, Tokyo, Japan). The mobile phase was 45% (v/v) acetonitrile containing 50 mmol/L sodium perchlorate, pH 3.6, and the flow rate was 0.2 mL/min. For coloumetric detection, the analytical and guard cells were set to +0.4 V and +0.45 V, respectively.
Determination of TBARS concentrations.
TBARS concentrations in serum were determined by the method of Yagi (27
), and those in tissues by the method of Ohkawa et al. (28
). The TBARS concentrations are presented as nmol malondialdehyde (MDA), using tetraethoxypropane as an external standard.
Data are presented as means ± SEM, n = 6. They were analyzed by one-way (Experiments 1 and 3) and two-way (Experiment 2) ANOVA with Fisher’s post-hoc test. In Experiment 2, the main effects are diet (deficient, -Toc, sesame) and feeding time (1, 3 and 7 d ). Mean values of -tocopherol concentrations of the -Toc and sesame groups in Experiment 1 were compared using Student’s t test. Differences with a P-value < 0.05 were regarded as significant.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Dietary -tocopherol or sesame seed did not affect the food intake, growth or liver weight of rats (data not shown). In the liver, kidney, brain and serum, the -tocopherol concentration of the sesame group was higher (P < 0.05) than that of the -Toc group (Fig. 1
), although the -tocopherol concentrations in the diets of the groups were the same. The -tocopherol concentration in the brain of the sesame group was higher (P < 0.05) than that of the -Toc group. The urinary excretion of -CEHC in the -Toc group was 30-fold greater than that of the deficient group, whereas that of the sesame group was 49% of that of the -Toc group (Fig. 2
). In the kidney and serum, TBARS concentrations of the sesame group were lower (P < 0.05) than those of the -Toc group (Fig. 3
).
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Dietary -tocopherol or sesame seed did not affect the food intake, growth or liver weight of rats on any day (Table 2
). The -tocopherol concentrations in the liver and serum of the -Toc group were higher (P < 0.05) than those of the deficient group, although the concentrations in the kidney and brain of the deficient and -Toc groups did not differ (P 
0.05) (Fig. 4
). The -tocopherol concentrations in the liver, kidney, brain and serum of the deficient and -Toc groups were unchanged from d 1 to 7. However, the -tocopherol concentrations in the liver, kidney, brain and serum of the sesame group were higher (P < 0.05) than those of the deficient and -Toc groups on d 1, 3 and 7. The concentrations in the tissues and serum of the sesame group were markedly elevated (P < 0.05) from d 1 to 7. The urinary excretion of -CEHC in the -Toc group was greater (P < 0.05) than those of the other groups during the experimental period (Fig. 5
). The amounts in the sesame and deficient groups did not differ (P 0.05) on d 1 and 3.
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Dietary -tocopherol, sesame seed, its lignans or ketokonazole did not affect the food intake, growth or liver weight of rats (data not shown). In the liver, kidney, brain and serum, the -tocopherol concentrations of the sesame, -Toc + sesamin and -Toc + sesaminol groups were higher (P < 0.05) than those of the deficient and -Toc groups (Fig. 6
). The -tocopherol concentrations of the sesame, -Toc + sesamin and -Toc + sesaminol groups did not differ (P 0.05). The urinary excretion of -CEHC in the -Toc group was 34-fold greater than that of the deficient group, and the amounts in the sesame, -Toc + sesamin and -Toc + sesaminol groups were 10, 20 and 33% of that of the -Toc group, respectively (Fig. 7
). In the liver, kidney, brain and serum, the -tocopherol concentrations of the -Toc + keto group were higher (P < 0.05) than that of the -Toc group (Fig. 6)
, and the urinary excretion of -CEHC in the -Toc + keto group was 19% of that of the -Toc group (Fig. 7)
.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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-tocopherol concentrations in the liver, kidney and plasma of rats (14
). Kiyose et al. (21
) showed recently that urinary excretion of -CEHC is the major route of -tocopherol metabolism in rats. In this study, we determined the urinary excretion of -CEHC in rats fed sesame seed for both long (28 d) and short (1, 3 and 7 d) periods, with the aim of clarifying the effect of dietary sesame lignans on tocopherol metabolism in vivo. Dietary sesame seed consumed over 28 d elevated -tocopherol concentrations in the liver, kidney, brain and serum (Fig. 1)
, and significantly decreased urinary excretion of -CEHC (Fig. 2)
.
Rats were fed a commercial diet, CE-2, for 7 d before the start of each experiment in this study. CE-2 contains 26.1 mg -tocopherol/kg diet and 7.9 mg -tocopherol/kg diet, and the -tocopherol concentrations in the tissues and blood of rats at the start of the experiments were high (12
). Supplementation of -tocopherol to the diet containing sesame seed inhibits the elevation of the -tocopherol concentration by sesame seed as described previously (16
). Therefore, rats were fed a diet without vitamin E for 28 d before Experiments 2 and 3 so that the effect of sesame seed or its lignans on -tocopherol metabolism could be determined clearly over a short period (1, 3 and 7 d). Dietary sesame seed completely inhibited the urinary excretion of -CEHC on d 1 and 3 (Fig. 5)
. The data suggest that the inhibition of -CEHC excretion by sesame seed causes an elevation of -tocopherol concentrations in the tissues and blood. The 200 g of sesame seed used in the experiments contains 50 mg of -tocopherol and 2 g of sesame lignans. In Experiment 3, we examined the effects of dietary sesamin and sesaminol, major lignans of sesame seed, on the urinary excretion of -CEHC in rats fed the diet containing 50 mg -tocopherol/kg and 2 g sesamin or sesaminol/kg. Dietary sesamin and sesaminol elevated the -tocopherol concentrations in the liver, kidney, brain and serum (Fig. 6)
, and decreased the urinary excretion of -CEHC (Fig. 7)
. The results indicate that dietary sesame seed elevates -tocopherol concentrations in the tissues and blood as a result of the inhibition of -CEHC excretion by its lignans.
Parker et al. (23
) and Birringer et al. (24
) recently reported that the oxidative catabolism of tocopherol to carboxychroman is catalyzed by CYP3A in HepG2 cells. We examined the effect of CYP3A on the -tocopherol metabolism in vivo using ketoconazole, a potent and selective inhibitor of CYP3A (23
). Dietary ketoconazole markedly decreased the urinary excretion of -CEHC (Fig. 7)
and elevated the -tocopherol concentrations in the tissues and serum of rats fed -tocopherol for 3 d (Fig. 6)
. The fact that the inhibition of CYP3A activity by dietary ketoconazole elevated -tocopherol concentrations in the tissues and blood suggests that -tocopherol is metabolized by CYP3A in vivo. Sesame lignans such as sesamin and sesaminol may be potent inhibitors of CYP3A, resulting in the elevation of -tocopherol concentrations in the tissues and blood.
Birringer et al. (24
) showed that -tocopherol metabolism by -oxidation is initiated by CYP3A in HepG2 cells. The inducible -oxidation is the rate-limiting step in the tocopherol metabolism. They reported that the competition of -oxidation with binding by -TTP determines the metabolic fate of tocopherol. In this study, a CYP3A inhibitor elevated -tocopherol concentrations in the tissues and blood in rats. These results indicate not only the affinity of vitamin E isoforms for -TTP but also that CYP3A activity regulates tocopherol metabolism. Vitamin E concentrations in the tissues and blood may be affected by food factors or compounds that change CYP3A activity.
It has been reported that the antioxidative effect of -tocopherol on lipid peroxidation in vitro is more potent than that of -tocopherol (1
–4
). Some reports have shown that the plasma concentration of -tocopherol (but not -tocopherol) is inversely correlated with the incidence of coronary heart disease (29
,30
). However, -tocopherol concentrations in the tissues and blood are extremely low (10
–12
). We showed that dietary sesame seed lowered the TBARS concentrations in the kidney and serum (Fig. 3)
. The data suggest that a high level of -tocopherol in certain tissues and blood acts as a potent antioxidant in vivo. -Tocopherol may be more effective as vitamin E than has been reported.
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ACKNOWLEDGMENTS |
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-CEHC in urine samples. |
FOOTNOTES |
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3 Abbreviations used: -TTP, -tocopherol transfer protein; CYP, cytochrome P450; -CEHC, 2,7,8-trimethyl-2(2'-carboxymethyl)-6-hydroxycroman; -Toc, -tocopherol; MDA, malondialdehyde; TBARS, thiobarbituric acid reactive substance.
Manuscript received 26 November 2001. Initial review completed 20 December 2001. Revision accepted 29 January 2002.
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LITERATURE CITED |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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1. Duthie, G. G., Gonzalez, B. M., Morrice, P. C. & Arthur, J. R. (1991) Inhibitory effects of isomers of tocopherol on lipid peroxidation of microsomes from vitamin E-deficient rats. Free Radic. Res. Commun. 15:35-40.[Medline]
2.
Saldeen, T., Li, D. & Mehta, J. L. (1999) Differential effects of - and -tocopherol on low-density lipoprotein oxidation, superoxide activity, platelet aggregation and arterial thrombogenesis. J. Am. Coll. Cardiol. 34:1208-1215.
3.
Cooney, R. V., Franke, A. A., Harwood, P. J., Hatch-Pigott, V., Custer, L. J. & Mordan, L. J. (1993) -Tocopherol detoxification of nitrogen dioxide: superiority to -tocopherol. Proc. Natl. Acad. Sci. U.S.A. 90:1771-1775.
4.
Christen, S., Woodall, A. A., Shigenaga, M. K., Southwell-Keely, P. T., Duncan, M. W. & Ames, B. N. (1997) -Tocopherol traps mutagenic electrophiles such as NOX and complements -tocopherol: physiological implications. Proc. Natl. Acad. Sci. U.S.A. 94:3217-3222.
5.
Bieri, J. G. & Evarts, R. P. (1974) Vitamin E activity of -tocopherol in the rat, chick and hamster. J. Nutr. 104:850-857.
6. Traber, M. G. & Sie, H. (1996) Vitamin E in humans: demand and delivery. Annu. Rev. Nutr. 16:321-347.[Medline]
7. Kayden, H. J. & Traber, M. G. (1993) Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans. J. Lipid Res. 34:343-358.[Medline]
8.
Ikeda, I., Imasato, Y., Sasaki, E. & Sugano, M. (1996) Lymphatic transport of -, - and -tocotrienols and -tocopherol in rats. Int. J. Vitam. Nutr. Res. 66:217-221.[Medline]
9. Traber, M. G. & Arai, H. (1999) Molecular mechanisms of vitamin E transport. Annu. Rev. Nutr. 19:343-355.[Medline]
10.
Burton, G. W., Traber, M. G., Acuff, R. V., Walters, D. N., Kayden, H., Hughes, L. & Ingold, K. U. (1998) Human plasma and tissue -tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E. Am. J. Clin. Nutr. 67:669-684.[Abstract]
11.
Behrens, W. A. & Madere, R. (1987) Mechanisms of absorption, transport and tissue uptake of RRR--tocopherol and d--tocopherol in the white rat. J. Nutr. 117:1562-1569.
12.
Ikeda, S., Toyoshima, K. & Yamashita, K. (2001) Dietary sesame seeds elevate - and -tocotrienol concentrations in skin and adipose tissue of rats fed the tocotrienol-rich fraction extracted from palm oil. J. Nutr. 131:2892-2897.
13.
Hosomi, A., Arita, M., Sato, Y., Kiyose, C., Ueda, T., Igarashi, O., Arai, H. & Inoue, K. (1997) Affinity for -tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. FEBS Lett. 409:105-108.[Medline]
14.
Yamashita, K., Nohara, Y., Katayama, K. & Namiki, M. (1992) Sesame seed lignans and -tocopherol act synergistically to produce vitamin E activity in rats. J. Nutr. 122:2440-2446.
15.
Lemcke-Norojärvi, M., Kamal-Eldin, A., Appelqvist, L.-Å., Dimberg, L. H., Öhrvall, M. & Vessby, B. (2001) Corn and sesame oils increase serum -tocopherol concentrations in healthy Swedish women. J. Nutr. 131:1195-1201.
16.
Yamashita, K., Iizuka, Y., Imai, T. & Namiki, M. (1995) Sesame seed and its lignans produce marked enhancement of vitamin E activity in rats fed a low -tocopherol diet. Lipids 30:1019-1028.[Medline]
17. Yamashita, K., Takeda, N. & Ikeda, S. (2000) Effects of various tocopherol-containing diets on tocopherol secretion into bile. Lipids 35:163-170.[Medline]
18.
Schultz, M., Leist, M., Petrzika, M., Gassmann, B. & Brigelius-Flohé, R. (1995) Novel urinary metabolite of -tocopherol, 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman, as an indicator of an adequate vitamin E supply?. Am. J. Clin. Nutr. 62:1527S-1534S.
19.
Swanson, J. E., Ben, R. N., Burton, G. W. & Parker, R. S. (1999) Urinary excretion of 2,7,8-trimethyl-2-(ß-carboxyethyl)-6-hydroxychroman is a major rout of elimination of -tocopherol in humans. J. Lipid Res. 40:665-671.
20.
Lodge, J. K., Ridlington, J., Leonard, S., Vaule, H. & Traber, M. G. (2001) - and -Tocotrienols are metabolized to carboxyethyl-hydroxychroman derivatives and excreted in human urine. Lipids 36:43-48.[Medline]
21.
Kiyose, C., Saito, H., Kaneko, K., Hamamura, K., Tomioka, M., Ueda, T. & Igarashi, O. (2001) -Tocopherol affects the urinary and biliary excretion of 2,7,8-trimethyl-2(2'-carboxyethyl)-6-hydroxychroman, -tocopherol metabolite, in rats. Lipids 36:467-472.[Medline]
22. Hattori, A., Fukushima, T. & Imai, K. (2000) Occurrence and determination of a natriuretic hormone, 2,7,8-trimethyl-2-(ß-carboxyethyl)-6-hydroxy chroman, in rat plasma, urine, and bile. Anal. Biochem. 281:209-215.[Medline]
23. Parker, R. S., Sontag, T. J. & Swanson, J. E. (2000) Cytochrome P4503A-dependent metabolism of tocopherols and inhibition by sesamin. Biochem. Biophys. Res. Commun. 277:531-534.[Medline]
24.
Birringer, M., Drogan, D. & Brigelius-Flohe, R. (2001) Tocopherols are metabolized in HepG2 cells by side chain -oxidation and consecutive ß-oxidation. Free Radic. Biol. Med. 31:226-232.[Medline]
25. American Institute of Nutrition (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J. Nutr. 123:1939-1951.
26. Ueda, T. & Igarashi, O. (1987) New solvent system for extraction of tocopherols from biological specimens for HPLC determination and the evaluation of 2,2,5,7,8-pentamethyl-6-chromanol as an internal standard. J. Micronutr. Anal. 3:185-198.
27. Yagi, K. (1976) A simple fluorometric assay for lipoperoxide in blood plasma. Biochem. Med. 15:212-216.[Medline]
28. Ohkawa, H., Ohishi, N. & Yagi, K. (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95:351-358.[Medline]
29. Ouml;hrvall, M., Sundlöf, G. & Vessby, B. (1996) Gamma, but not alpha, tocopherol levels in serum are reduced in coronary heart disease patients. J. Intern. Med. 239:111-117.[Medline]
30.
Kontush, A., Spranger, T., Reich, A., Baum, K. & Beisiegel, U. (1999) Lipophilic antioxidants in blood plasma as markers of atherosclerosis: the role of -carotene and -tocopherol. Atherosclerosis 144:117-122.[Medline]
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