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Objectives To (1) describe micronutrient intakes among women of reproductive age living in Mumbai slums; (2) assess the adequacy of these intakes compared with reference values; (3) identify important dietary sources of micronutrients. Subjects/methods Participants were 6426 non-pregnant women aged 16-39 years, registered in a randomised controlled trial of a food-based intervention set in the Bandra, Khar and Andheri areas of Mumbai, India. Cross-sectional quantified food frequency questionnaire (FFQ) data were collected. Vitamin (n = 9) and mineral (n = 6) intakes were calculated and analysed in relation to dietary reference values (DRVs). Important dietary sources were identified for each micronutrient. Results Median intakes of all micronutrients, except vitamin E, were below the FAO/WHO reference nutrient intake (RNI). Intakes of calcium, iron, vitamin A and folate were furthest from the RNI. For seven of the micronutrients, over half of the women had intakes below the lower reference nutrient intake (LRNI); this figure was over 75% for calcium and riboflavin. The majority of women (93%) had intakes below the EAR for 5 or more micronutrients, and 64% for 10 or more. Adolescents had lower intakes than women aged >19 years. Less than 1% of adult women and no adolescents met the EAR for all micronutrients. Animal source foods and micronutrient-rich fruit and vegetables were consumed infrequently. Conclusions These women had low intakes of multiple micronutrients, increasing their risk of insufficiency. There is a need to determine the factors causing poor intakes, to direct interventions that improve diet quality and nutritional sufficiency., Author(s): Rebecca L. Nunn [sup.1], Sarah H. Kehoe [sup.1], Harsha Chopra [sup.2], Sirazul A. Sahariah [sup.2], Meera Gandhi [sup.2], Chiara Di Gravio [sup.1], Patsy J. Coakley [sup.1], Vanessa A. Cox [...]

Our objective in this study was to determine whether a mitochondda-targeted vitamin E derivative (MitoVit E) would decrease oxidative stress and associated obesity by preventing a previously proposed aconitase inhibition cascade. Sixty-four mice were fed a high-fat (HF) diet for 5 wk. They were then switched to either a low-fat (LF) or a medium-fat (MF) diet and gavaged with MitoVit E (40 mg MitoVit E kg body [weight.sup.-1]) or drug vehicle (10% ethanol in 0.9% NaCl solution) every other day for 5 wk. Epididymal fat weight, as well as liver lipid and remaining carcass lipid, were significantly lower in the MF group receiving MitoVit E (MF-E) than in the MF group receiving vehicle only (MF-C). Liver mitochondrial [H.sub.2][O.sub.2] production and the protein carbonyl level were also significantly lower in MF-E than in MF-C mice. In contrast, none of the biochemical variables (aconitase activity, ATP and [H.sub.2][O.sub.2] production, and protein carbonyl level) in the muscle mitochondria were modified by MitoVit E in either MF or LF groups. Expression of acetyl-CoA carboxylase and fatty acid synthase in both liver and adipose tissue of MF groups was not affected by MitoVit E. However, expression of carnitine palmitoyltransferase 1 a in the liver and uncoupling protein 2 in adipose tissue were significantly enhanced by MitoVit E in both LF and MF groups. In conclusion, MitoVit E attenuates hepatic oxidative stress and inhibits fat deposition in mice but not through alleviation of the aconitase inhibition cascade. doi: 10.3945/jn.110.121715.

The aim of this experiment was to clarify the contribution of the [alpha]-tocopherol transfer activity of lipoprotein lipase (LPL) to vitamin E transport to tissues in vivo. We studied the effect of Triton WR1339, which prevents the catabolism of triacylglycerol-rich lipoproteins by LPL on vitamin E distribution in rats. Vitamin E-deficient rats fed a vitamin E-free diet for 4 wk were injected with Triton WR1339 and administered by oral gavage an emulsion containing 10 mg of [alpha]-tocopherol, 10 mg of [gamma]-tocopherol, or 29.5 mg of a tocotrienol mixture with 200 mg of sodium taurocholate, 200 mg of triolein, and 50 mg of albumin, [alpha]-Tocopherol was detected in the serum and other tissues of the vitamin E-deficient rats, but [gamma]-tocopherol, [alpha]- and [gamma]-tocotrienol were not detected. Triton WR1339 injection elevated (P < 0.05) the serum [alpha]-tocopherol concentration and inhibited (P < 0.05) the elevation of [alpha]-tocopherol concentration in the liver, adrenal gland, and spleen due to the oral administration of [alpha]-tocopherol. Neither [alpha]-tocopherol administration nor Triton WR1339 injection affected (P [greater than or equal to] 0.05) the [alpha]-tocopherol concentration in the perirenal adipose tissue, epididymal fat, and soleus muscle despite a high expression of LPL in the adipose tissue and muscle. These data show that [alpha]-tocopherol transfer activity of LPL in adipose tissue and muscle is not important for [alpha]-tocopherol transport to the tissue after [alpha]-tocopherol intake or that the amount transferred is small relative to the tissue concentration. Furthermore, Triton WR1339 injection tended to elevate the serum [gamma]-tocopherol (P= 0.071) and [alpha]-tocotrienol (P = 0.053) concentrations and lowered them (P < 0.05) in the liver and adrenal gland of rats administered [gamma]-tocopherol or [alpha]-tocotrienol. These data suggest that lipolysis of triacylglycerol-rich chylomicron by LPL is necessary for postprandial vitamin E transport to the liver and subsequent transport to the other tissues.

Vitamin E is an essential nutrient for humans and is obtained primarily from food, especially oil, derived from the seed of plants. Genes encoding the committed steps in vitamin E synthesis in plants (VTE, loci 1-5) have been isolated and used for tocopherol pathway engineering with various degrees of success. As a complement to such approaches we have used quantitative trait loci analysis with two sets of Arabidopsis thaliana recombinant inbred lines and have identified 14 QVE (quantitative vitamin E) loci affecting tocopherol content and composition in seeds. Five QVE intervals contain VTE loci that are likely QVE gene candidates. Nine QVE intervals do not contain VTE loci and therefore identify novel loci affecting seed tocopherol content and composition. Several near-isogenic lines containing introgressions of the accession with increased vitamin E levels were shown to confer significantly elevated tocopherol levels compared with the recurrent parent. Fine-mapping has narrowed QVE7 (a [gamma]-tocopherol quantitative trait loci) to an 8.5-kb interval encompassing two genes. Understanding the basis of the QVE loci in Arabidopsis promises to provide insight into the regulation and/or metabolism of vitamin E in plants and has clear ramifications for improving the nutritional content of crops through marker-assisted selection and metabolic engineering. biofortification | quantitative trait loci | seed metabolism | tocopherol

Previous studies comparing the biokinetics of deuterated natural (RRR) and synthetic (all-rac) [alpha]-tocopherol (vitamin E) used a simultaneous ingestion or competitive uptake approach and reported relative bioavailability ratios close to 2:1, higher than the accepted biopotency ratio of 1.36:1. The aim of the current study was to compare the biokinetics of deuterated natural and synthetic vitamin E using a noncompetitive uptake model both before and after vitamin E supplementation in a distinct population. Healthy men (n = 10) carrying the apolipoprotein (apo)E4 genotype completed a randomized crossover study, comprised of two 4-wk treatments with 400 mg/d (RRR-[alpha]-tocopheryl and all-rac-[alpha]-tocopheryl acetate) with a 12-wk washout period between treatments. Before and after each treatment period, the subjects consumed a capsule containing 150 mg deuterated [alpha]-tocopheryl acetate in either the RRR or all-rac form depending on their treatment regimen. Blood was obtained up to 48 h after ingestion, and tocopherols analyzed by LC/MS. After deuterated all-rac administration, plasma deuterated tocopherol maximum concentrations and area under the concentration vs. time curves (AUC) were lower than those following RRR administration. The RRR:all-rac ratios determined from the deuterated biokinetic profiles (maximum concentration; [C.sub.max]) and AUCs were 1.35:1 [+ or -] 0.17 and 1.33:1 [+ or -] 0.18, respectively. The 4-wk supplementation with either RRR or all-rac significantly increased plasma [alpha]-tocopherol concentrations (P < 0.001), but decreased the plasma response to newly absorbed deuterated RRR or all-rac [alpha]-tocopherol. Using a noncompetitive uptake approach, the relative bioavailability of natural to synthetic vitamin E in apoE4 males was close to the currently accepted biopotency ratio of 1.36:1. KEY WORDS: * tocopherol * natural * synthetic * biokinetics * bioavailability * apoE4

Previous studies have shown that deficiencies in selenium (Se) and/or vitamin E (VE) can exacerbate the infectivity and pathogenesis of coxsackievirus B3 and influenza. Both Se and VE play a role in immune function and antioxidant defense. To determine whether these deficiencies would affect the normal course of infection with a metazoan parasite, mice were made deficient in Se and/or VE and inoculated with the gastrointestinal nematode parasite Heligmosomoides polygyrus. Both primary and secondary infections were assessed. Although the course of a primary infection with H. polygyrus was unaffected by diet, diets deficient in Se, VE, and both Se and VE (Se/VE double-deficiency) all caused delayed adult worm expulsion and increased fecundity during a secondary infection; suggesting an impaired intestinal response. H. polygyrus-induced IL-4 levels were diet-independent; but Se/VE double-deficiency blocked the H. polygyrus-induced IL-4 receptor-associated decrease in sodium-dependent glucose absorption in the jejunum that contributes to worm expulsion. In contrast, Se/VE double-deficiency had no effect on the infection-induced, IL-4R-associated increase in epithelial cell permeability that accompanies the infection. These results suggest that both Se and VE are required for specific IL-4-related changes in intestinal physiology that promote host protection against H. polygyrus. KEY WORDS: * selenium * vitamin E * parasite * immunity * gastrointestinal

Vitamin E is a lipophilic chain-breaking antioxidant that prevents lipid peroxidation. Although cigarette smoke is a potent source of oxidative stress that depletes vitamin E in vitro, it is unclear whether it has a similar effect in vivo, particularly in humans. Therefore, this review will discuss the role of cigarette smoke on [gamma]-tocopherol ([gamma]-T) nitration, its effect on [alpha]-tocopherol ([alpha]-T) biokinetics in smokers, and the changes in the synthesis, plasma concentrations, and urinary excretion of the vitamin E metabolite (CEHC; carboxy-ethyl-hydroxy-chroman). Last, the possibility of CEHC as a biomarker of vitamin E status will be assessed as will the question whether smokers have increased dietary requirements of vitamin E.

In this study, the effect of dietary vitamin E on the hepatic tumor-promoting activity of PCB-77 and PCB-153 in female Sprague-Dawley rats (175-200 g) was investigated. One week after diethylnitrosamine injection, rats were fed purified diets containing 10, 50, or 250 mg/kg vitamin E in the form of [alpha]-tocopheryl acetate. Starting 1 wk later, we injected rats i.p. with vehicle (corn oil) or PCB-77 or PCB-153 (300 [micro]mol/kg) every 14 d for 4 injections. All rats were killed 10 d after the last PCB injection. The number and volume of placental glutathione S-transferase (PGST)-positive foci were increased by PCB-77 but not by PCB-153. Vitamin E did not affect the induction of PGST-positive foci. PCB-77, but not PCB-153, increased hepatic NF-[kappa]B activity. In conclusion, dietary vitamin E supplementation does not protect against the induction of altered hepatic focal lesions by PCBs. KEY WORDS: * polychlorinated biphenyls * vitamin E * altered hepatic foci * NF-[kappa]B

During a study of the effect of vitamin E in activated mouse macrophages, we observed a reduction in the viability of cells treated with various forms of vitamin E. We show this report that some tocopherols (both [gamma]- and [delta]-tocopherol) are cytotoxic to some but not all cell types. Mouse macrophages were especially sensitive (40 [micro]mol/L), whereas human hepatocytes and bovine endothelial cells were almost completely refractory (90 [micro]mol/L). The fully methylated tocopherol, [alpha]-tocopherol ([alpha]-Toc), was not cytotoxic in any cell type tested. The cytotoxicity observed with [delta]-tocopherol ([delta]-Toc) was associated with 2 markers of apoptosis. Vitamer-specific cytotoxicity was not due to differences in cellular uptake/accumulation because both [alpha]-Toc and [delta]-Toc accumulated equally in any cell type tested. In contrast, the cell-specific cytotoxicity was related in part to uptake/accumulation of the tocopherols. Macrophages accumulated nearly 5 times more tocopherol compared with hepatocytes cultured under similar conditions. To address the hypothesis that uptake accounted for the cell-specific sensitivity, we developed a macrophage 'subtype' that was markedly resistant (>150 [micro]mol/L) to [delta]-Toc. Under many different cell culture conditions (including human serum) uptake/accumulation of tocopherols was reduced in this subtype by ~50%. Further selection and evaluation of this phenotype, however, demonstrated no cytotoxicity even when cellular levels were elevated. Our results show that undermethylated tocopherols are cytotoxic to macrophages and that there are independent and selectable processes that determine cellular tocopherol uptake/accumulation and [delta]-Toc cytotoxicity. KEY WORDS: * tocopherol * macrophage * cellular accumulation * vitamin E * toxicity

Epidemiological studies suggest that consumption of vegetables rich in the xanthophylls lutein (LUT) and zeaxanthin (ZEA) reduces the risk for developing age-related cataract, a leading cause of vision loss. Although LUT and ZEA are the only dietary carotenoids present in the lens, direct evidence for their photoprotective effect in this organ is not available. The present study examined the effects of xanthophylls and [alpha]-tocopherol ([alpha]-TC) on lipid peroxidation and the mitogen-activated stress signaling pathways in human lens epithelial (HLE) cells following ultraviolet B light (UVB) irradiation. When presented with LUT, ZEA, astaxanthin (AST), and [alpha]-TC as methyl-[beta]-cyclodextrin complexes, HLE cells accumulated the lipophiles in a concentration- and time-dependent manner with uptake of LUT exceeding that of ZEA and AST. Pretreatment of cultures with either 2 [micro]mol/L xanthophyll of 10 [micro]mol/L [alpha]-TC for 4 h before exposure to 300 J/[m.sup.2] UVB radiation decreased lipid peroxidation by 47-57% compared with UVB-treated control HLE cells. Pretreatment with the xanthophylls and [alpha]-TC also inhibited UVB-induced activation of c-JUN N[H.sub.2]-terminal kinase (JNK) and p38 by 50-60 and 25-32%, respectively. There was substantial inhibition of UVB-induced JNK and p38 activation for cells containing 2.3 nmol [alpha]-TC/mg protein was required to significantly decrease UVB-induced stress signaling. These data suggest that xanthophylls are more potent than [alpha]-TC for protecting human lens epithelial cells against UVB insult. KEY WORDS: * lutein * zeaxanthin * MAPK stress signaling * lipid peroxidation * human lens epithelial cells

Oxidized fats affect animal metabolism in several ways. To gain a comprehensive understanding of the molecular mechanisms underlying the effects of dietary oxidized rats in rats at varying dietary vitamin E concentrations, the gene expression profile of the liver was monitored with an array containing 1176 binding sites for cDNAs. Rats were fed diets with a fresh fat and vitamin E concentrations of 25 or 250 mg [alpha]-tocopherol/kg (FF25, FF250 rats) or a fat heated at 50[degrees]C for 38 d, with vitamin E concentrations of 25 or 250 mg [alpha]-tocopherol/kg (OF25, OF250 rats) for 63 d. Differences in gene expression were considered to be significant at a ratio of at least 1.4. In the OF25 rats, the expression of 47 genes was altered; in the OF250 rats, the expression of 37 genes was altered, and in the FF250 rats, the expression of 21 genes was altered compared with FF25 rats. In both OF25 and OF250 rats, a series of target genes of the peroxisome proliferator-activated receptor [alpha] (PPAR[alpha]) was upregulated. Determination of gene expression of acyl CoA oxidase and activity of catalase confirmed that oxidized fats caused peroxisome proliferation in the liver. In OF25 and OF250 rats, there was also upregulation of 12 and 5 genes involved in xenobiotic metabolism and stress response, of 7 and 7 genes involved in protein metabolism, of 5 and 2 genes encoding intracellular effectors or modulators and of 5 and 6 genes, respectively, encoding activators or repressors of transcription or translation. In conclusion, this study provides indirect evidence that dietary oxidized fats cause an activation of the PPAR[alpha], irrespective of the dietary vitamin E concentration. Identification of several other differentially regulated genes may be helpful to understand the effects of oxidized rats on animal metabolism. KEY WORDS: * rats * oxidized rats * vitamin E * cDNA array * gene expression

We showed previously that dietary antioxidant depletion enhances tumor reactive oxygen species (ROS) and apoptosis, resulting in a reduction in brain tumor size in the [TgT.sub.121] transgenic mouse model, a nonmetastatic tumor model. Here, in a transgenic mouse model of mammary tumorigenesis with defined rates of tumor growth and lung-targeted metastasis, we determined the ability of dietary antioxidant depletion to inhibit tumor growth and metastasis. Compared with control mice fed a standard diet, antioxidant-depleted mice exhibited tumor-targeted generation of ROS manifested by increased levels of oxidatively modified DNA/RNA (8-hydroxy-2'-deoxyguanine, 8-hydroxyguanine) and lipid peroxidation (4-hydroxy-2-nonenal) in primary and metastatic tumor foci. In addition to increased tumor-targeted ROS, the number of apoptotic cells was increased approximately 500% (P < 0.01) and terminal dUTP nucleotide DNA end-labeling-positive cells 200% (P < 0.01) in mice fed the antioxidant-depleted diet, whereas the percentage of tumor cells undergoing mitosis was >50% lower than in controls (P < 0.01). The proportional distribution of small ( KEY WORDS: * antioxidant * apoptosis * mammary neoplasm * metastasis * reactive oxygen species

Aim: To investigate the effect of vitamin C and E supplementation in the levels of nitrite, nitric oxide (NO) related metabolite, and ocular surface parameters in diabetic patients. Methods: 50 [...]

A new vitamin E constituent having an unusual methylene unsaturation at the isoprenoid-chain terminus of [alpha]-tocopherol ([alpha]-Toc) was isolated from chum salmon eggs and was found to have identical antioxidant activity as does [alpha]-Toc in methanol or liposomal suspension at 37 [degrees] C. Here we report that this marine-derived tocopherol (MDT) is broadly distributed with [alpha]-Toc in the tissue of marine fish, and that the MDT composition of total vitamin E is greater in the flesh of cold-water salmon (12-20%) than in that of tropical fish ([less than or equal to] 2.5%). Vitamin E analysis of cultured masu salmon maintained on a MDT-deplete diet showed substantially less MDT content than native masu salmon, suggesting atrophic origin of MDT. This contention is supported by the finding of MDT in marine plankton from the cold waters of Hokkaido. We found that MDT inhibited peroxidation of cholesterol-containing phosphatidylcholine liposomes to a greater extent than did [alpha]-Toc at 0 [degrees] C. Furthermore, the ratios of the rate constants for MDT and [alpha]-Toc to scavenge peroxyl radicals increased with decreasing rates of radical flux in liposomes and fish oil at 0 [degrees] C, indicating that the enhanced activity of MDT at low temperature is attributed to its greater rate of diffusion in viscous lipids. These results suggest that MDT production, or its trophic accumulation, may reduce lipid peroxidation in marine organisms functionally adapted to cold-water environments.

The synthesis of photoaffinity labels of alpha-tocopherol are prepared from alkenols by reduction with (sup)3H(sub)2 in one-pot protocol.

The link between plasma antioxidants beta-carotene and alpha-tocopherol, and lung function in Dutch adults aged between 20 and 59 has been studied. It was found that those with a high plasma beta-carotene had a higher forced vital capacity (FVC) than those with a low plasma beta-carotene concentration. The difference for forced expiratory volume (FEV) between high and low rates of plasma beta-carotene tended towards a similar positive direction.

Blood plasma gamma-tocopherol (TOH) concentrations are lower at birth than in later life, according to research into the relationships between levels of tocopherols, retinol and carotenoids in maternal and umbilical cord blood plasma. Cholesterol and triglyceride levels were found to be lower in cord plasma than in maternal plasma. There was a strong link between cord plasma TOHs and cholesterol and triglycerides. There was no connection between maternal and cord plasma x-TOH levels.

The effects of oral doses of canthaxanthin on tissue distribution of [Alpha]- and [Gamma],-tocopherols were investigated in three experiments in male and female Balb/c mice. Mice were assigned to receive canthaxanthin [7 or 14 [[micro]gram]/(g body weight * d)] or placebo (olive oil) by gavage for different periods of time (0, 1, 2, 4 and 6 wk). A 2 wk-treatment with canthaxanthin resulted in incorporation of the carotenoid in all tissues analyzed, including liver, spleen, kidney, lung and heart. In liver, the maximum accumulation of the carotenoid was reached after 2 wk of dosing in female mice and after 6 wk in male mice. Canthaxanthin incorporation was accompanied by changes in [Alpha]- and -[Gamma]-tocopherol concentrations in plasma and tissues. These included the following: 1) a significant increase (P < 0.001) in [Alpha]-tocopherol concentration in spleen (21 and 27% in male and female mice, respectively) after 2 wk and in liver ([approximately]50% in both male and female mice) after 6 wk; 2) a significant decrease in [Gamma]-tocopherol concentration in plasma (P < 0.05) and tissues (P < 0.001) after 2 wk of treatment. In female mice, this decrease was 55% in plasma, 45% in liver, 44% in kidney, 71% in lung and 70% in heart. In male mice, the decrease was observed only in plasma (30%), kidney (54%) and heart (46%). In liver, the decrease in [Gamma]-tocopherol concentration was both dose- and time-dependent and significantly (P < 0.001) greater in female than in male mice. We conclude that dietary administration of canthaxanthin modifies tocopherol status in murine tissues. KEY WORDS: * canthaxanthin * [Alpha]-tocopherol * [Gamma]-tocopherol * mice * tissue distribution

Copper-zinc superoxide dismutase (Cu,ZnSOD) is the antioxidant enzyme that catalyzes the dismutation of superoxide [Mathematical Expression Omitted] to [O.sub.2] and [H.sub.2][O.sub.2]. In addition, Cu,ZnSOD also exhibits peroxidase activity in the presence of [H.sub.2][O.sub.], leading to self-inactivation and formation of a potent enzyme-bound oxidant. We report in this study that lipid peroxidation of L-[Alpha]-lecithin liposomes was enhanced greatly during the SOD/[H.sub.2][O.sub.2] reaction in the presence of nitrite anion (N[O.sub.[2.sup.-]]) with or without the metal ion chelator, diethylenetriaminepentacetic acid. The presence of N[O.sub.[2.sup.-]] also greatly enhanced [Alpha]-tocophenol ([Alpha]-TH) oxidation by SOD/[H.sub.2][O.sub.2] in saturated 1,2-dilauroyl-sn-glycero-3-phosphatidylcholine liposomes. The major product identified by HPLC and UV-studies was [Alpha]-tocopheryl quinone. When 1,2-diauroyl-sn-glycero-3-phosphatidylcholine liposomes containing [Gamma]-to-copherol ([Gamma]-TH) were incubated with SOD/[H.sub.2][O.sub.2]/N[O.sub.[2.sup.-]], the major product identified was 5-N[O.sub.2]-[Gamma]-TH. Nitrone spin traps significantly inhibited the formation of [Alpha]-tocopheryl quinone and 5-N[O.sub.2]-[Gamma]-TH. N[O.sub.[2.sup.-]] inhibited [H.sub.2][O.sub.2]-dependent inactivation of SOD. A proposed mechanism of this protection involves the oxidation of N[O.sub.[2.sup.-]] by an SOD-bound oxidant to the nitrogen dioxide radical [Mathematical Expression Omitted]. In this study, we have shown a new mechanism of nitration catalyzed by the peroxidase activity of SOD. We conclude that N[O.sub.[2.sup.-]] is a suitable probe for investigating the peroxidase activity of familial Amyotrophic Lateral Sclerosis-linked SOD mutants.

The effect of a short-term, high-dose intramuscular injection of d-[Alpha]-tocopherol was studied in pigs given a challenge dose of lipopolysaccharide (LPS). Twenty-four pigs surgically fitted with jugular catheters were used in a 2 x 2 factorial design. Pigs received either 0 or 600 mg d-[Alpha]-tocopherol by intramuscular injection for 3 d before receiving an intraperitoneal injection of saline containing either 0 or 5 [[micro]gram]/kg body weight Escherichia coil LPS. Blood was collected from indwelling jugular catheters at 0, 1, 2, 4, 6, 8, 12 and 24 h after injection of LPS. Plasma [Alpha]-tocopherol levels were 13-fold greater (P < 0.01) at time 0 in pigs pretreated with 600 mg d-[Alpha]-tocopherol (9.9 [+ or -] 1.3 mg/L) than in those not treated with d-[Alpha]-tocopherol (0.74 [+ or -] 0.09 mg/L). Injection of LPS increased (P < 0.05) plasma levels of interleukin-6 (IL-6) and cortisol at 2-h postinjection, regardless of vitamin E treatment. However, pigs that received [Alpha]-tocopherol before the LPS challenge had substantially lower (P < 0.05) peak levels of IL-6 and cortisol than pigs not receiving [Alpha]-tocopherol. These results suggest that supplementation with a surfeit level of vitamin E reduces the response of pigs to endotoxin. KEY WORDS: * vitamin E * lipopolysaccharide * interleukin-6 * cortisol * pigs

The reaction of superoxide (a reactive oxygen species) and nitric oxide (one of the nitrogen oxides with numerous biological functions) results in the production of peroxynitrite. The characteristics of oxidation of [Alpha]-tocopherol (vitamin E) in synaptosomes (nerve ending particles) and mitochondria by peroxynitrite were studied. The subcellular fractions were isolated from brain hemispheres of 4-month-old male Fischer 344 rats by standard centrifugation procedures involving Ficoll gradients. Peroxynitrite treatment oxidized [Alpha]-tocopherol in KEY WORDS: rats brain vitamin E tocopherol oxidation peroxynitrite

Vitamin E ([Alpha]-tocopherol) is a fat-soluble antioxidant that is transported by plasma lipoproteins in the body. [Alpha]-Tocopherol taken up by the liver with lipoprotein is thought to be resecreted into the plasma in very low density lipoprotein (VLDL). [Alpha]-Tocopherol transfer protein ([Alpha]TTP), which was recently identified as a product of the causative gene for familial isolated vitamin E deficiency, is a cytosolic liver protein and plays an important role in the efficient recycling of plasma vitamin E. To throw light on the mechanism of [Alpha]TTP-mediated [Alpha]-tocopherol transfer in the liver cell, we devised an assay system using the hepatoma cell line McARH7777. Using this system, we found that the secretion of [Alpha]-tocopherol was more efficient in cells expressing [Alpha]TTP than in matched cells lacking [Alpha]TTP. Brefeldin A, which effectively inhibits VLDL secretion by disrupting the Golgi apparatus, had no effect on [Alpha]-tocopherol secretion, indicating that [Alpha]TTP-mediated [Alpha]-tocopherol secretion is not coupled to VLDL secretion. Among other agents tested, only 25-hydroxycholesterol, a modulator of cholesterol metabolism, inhibited [Alpha]tocopherol secretion. This inhibition is most likely mediated by oxysterol-binding protein. These results suggest that [Alpha]TTP present in the liver cytosol functions to stimulate secretion of cellular [Alpha]-tocopherol into the extracellular medium and that the reaction utilizes a novel non-Golgi-mediated pathway that may be linked to cellular cholesterol metabolism and/or transport.

Dietary intakes of retinol equivalents, [Alpha]-tocopherol equivalents, vitamin D and phylloquinone were estimated from three sets of 4-d weighed diet records and compared to three corresponding fasting plasma concentrations of retinol, 25-hydroxyvitamin D, [Alpha]-tocopherol, and phylloquinone measured in 34 healthy adults over 20 wk. The magnitude of the correlation between dietary vitamin intake and its corresponding biochemical measure is in part determined by the reproducibility of each of the measures, so within-to-between subject variance ratios were calculated for both dietary intakes and plasma concentrations. Phylloquinone was the only fat-soluble vitamin with a significant correlation between dietary intake and fasting plasma concentration (r = 0.51, P = 0.004). This correlation improved with an increase in both the number of independent diet records and independent plasma measures. Of the dietary intake measures, all the fat-soluble vitamins had greater within than between subject variance, with the highest measured for phylloquinone (6.86:1). Of the plasma measures, only phylloquinone had a within-to-between subject variance ratio greater than one (5.36:1). Comparisons across age and sex for dietary intake and plasma concentrations differed in pattern among the fat-soluble vitamins. KEY WORDS: * vitamin A * vitamin D * vitamin E * vitamin K * humans

Antioxidants may play an important role in preventing free radical damage associated with aging by interfering directly in the generation of radicals or by scavenging them. We investigated the effects of a high vitamin E and/or a high [Beta]-carotene diet on aging of the anion transporter, band 3, in lymphocytes and brain. The band 3 proteins function as anion transporters, acid base regulators, C[O.sub.2] transporters, and structural proteins that provide a framework for membrane lipids and that link the plasma membrane to the cytoskeleton. Senescent cell antigen (SCA), which terminates the life of cells, is a degradation product of band 3. This study was conducted as a double-blind study in which eight groups of middle-aged or old mice received either high levels of [Beta]-carotene and/or vitamin E or standard levels of these supplements in their diets. Anion transport kinetic assays were performed on isolated splenic lymphocytes. Immunoreactivity of an antibody that recognizes aging changes in old band 3 preceding generation of SCA was used to quantitate aged band 3 in brain tissue. Results indicate that vitamin E prevented the observed age-related decline in anion transport by lymphocytes and the generation of aged band 3 leading to SCA formation. [Beta]-Carotene had no significant effect on the results of either assay. Since increased aged band 3 and decreased anion transport are initial steps in band 3 aging, which culminates in the generation of SCA and cellular removal, vitamin E prevents or delays aging of band 3-related proteins in lymphocytes and brain.

A plausible hypothesis and a model has been proposed to facilitate the understanding of the inhibitory properties of vitamin E quinone, an anticoagulant having beneficial effects on stroke and ischemic heart disease. Vitamine E is a potent inhibitor of vitamin K-dependent carboxylase. The model supports the interpretation of the anticlotting activity associated with vitamin E. This consideration of the vitamin E as an anticlotting agent is discussed.

Hydrogen atom transfer from the 5-methyl group of one radical to the phenoxyl oxygen atom of the other occurs during the rate determining step in the bimolecular self-reaction of alpha-tocopheroxyl (alpha-TO) radicals to produce alpha-tocopherol and o-quinone methide. The rate constants can vary from a factor of 7 in a single experiment at 37 degrees celsius and the abnormal behavior of alpha-TO is due to the presence of a small bisphenol. Two o-quinone methide molecules couple to produce a spiro-dimer which is then reduced, most likely by an unoxidized alpha-tocopherol, to form bisphenol.