Affinity for α‐tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs

Hosomi, Akihiro; Arita, Makoto; Sato, Yuji; Kiyose, Chikako; Ueda, Tadahiko; Igarashi, Osamu; Arai, Hiroyuki; Inoue, Keizō

doi:10.1016/s0014-5793(97)00499-7

Cited by 584 publications

(421 citation statements)

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“…Hoppe and Krennrich (2000) and Stone et al (2003) found similar results in humans. This is because of the higher affinity of the α-tocopherol transfer protein for the single stereoisomer (-RRR) of natural vitamin E, against the equimolar amounts of the other eight isomers presented in the synthetic form (Hosomi et al, 1997). Furthermore, it is of interest to highlight that the α-tocopherol stereoisomer profile reflects the vitamin E source provided to sows to a higher extent than that supplied to piglets after weaning.…”

Section: Resultsmentioning

confidence: 99%

Effects of oral micellized natural vitamin E (d-α-tocopherol) v. synthetic vitamin E (dl-α-tocopherol) in feed on α-tocopherol levels, stereoisomer distribution, oxidative stress and the immune response in piglets

Amazán

Cordero

López‐Bote

et al. 2014

Animal

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This study evaluated the strategy of supplementing oral micellized natural vitamin E (D-α-tocopherol) to either piglets and/or sows on α-tocopherol concentrations in piglets serum and tissues after weaning. One first experiment tested the influence of the vitamin E supplementation source (natural form in water v. the synthetic form in feed) and dose administered to piglets and/or sows on serum α-tocopherol concentration, α-tocopherol stereoisomer accumulation, antioxidant capacity and immune response of weaned piglets. A second experiment studied the effect of sow source and dose vitamin E supplementation on some of these parameters in piglets. Oral supplementation to sows with natural vitamin E as a micellized form (D-α-tocopherol) at the lowest dose produced a similar concentration of α-tocopherol in serum at days 2, 14 and 28 postpartum to those supplemented with threefold higher dose of the synthetic form in feed. At day 39 of age, neither piglet supplementation source nor dose significantly affected α-tocopherol accumulation in the serum, muscle, subcutaneous fat or liver. Those piglets from sows supplemented with the micellized alcohol form had higher RRR-α-tocopherol stereoisomers (P < 0.001) and lower (P < 0.001) RRS-RSS-and RSR-α-tocopherol, at day 39 of age than those from sows supplemented with the synthetic form. A predominant importance of sow over piglet vitamin E supplementation was observed on stereoisomer distribution in piglets. Low doses of oral natural vitamin E supplementation to sows or piglets did not increase the oxidative stress of piglets when compared with the use of the synthetic form in feed. Immunoglobulin levels in piglet serum at day 39 were not affected by natural vitamin E supplementation at low doses in drinking water of piglets or sows when compared with the synthetic form in feed. IgA tended to be higher (P = 0.145) at day 39 in piglets supplemented with natural vitamin E when compared with those supplemented with the synthetic form. Low doses of oral micellized natural vitamin E supplementation to sows is an interesting feeding strategy, when compared with the use of high doses of the synthetic form in feed, because it results in similar α-tocopherol concentrations, allows a predominant -R stereoisomer distribution in piglets and also maintains their oxidative status in vivo.Keywords: immune response, micellized natural α-tocopherol, oxidative status, sows and piglets, stereoisomers ImplicationsThe natural form of vitamin E is preferentially accumulated by sows and piglets. In the present study, we show that micellized D-α-tocopherol added to sows in water at threefold lower doses than the synthetic form (DL-α-tocopherol) in feed allows to reach similar α-tocopherol concentration and a predominant -R stereoisomer distribution in piglets. The present paper contributes to better understanding the oral natural vitamin E needs of the sow and piglets during gestation and lactation period.

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Section: Resultsmentioning

confidence: 99%

Effects of oral micellized natural vitamin E (d-α-tocopherol) v. synthetic vitamin E (dl-α-tocopherol) in feed on α-tocopherol levels, stereoisomer distribution, oxidative stress and the immune response in piglets

Amazán

Cordero

López‐Bote

et al. 2014

Animal

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“…For the vitamin E molecules introduced with the diet, these responses depend on specific pathways that are under the influence of the hepatic a-tocopherol transfer protein (a-TTP). As prototype vitamin E binding protein that regulates uptake and trafficking of all the vitamers in liver cells (Morley et al 2008), this protein binds the fully methylated and saturated form a-TOH with at least 10-fold higher affinity than HM and all the T3 forms (Hosomi et al 1997).…”

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confidence: 99%

Why tocotrienols work better: insights into the in vitro anti-cancer mechanism of vitamin E

et al. 2011

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The selective constraint of liver uptake and the sustained metabolism of tocotrienols (T3) demonstrate the need for a prompt detoxification of this class of lipophilic vitamers, and thus the potential for cytotoxic effects in hepatic and extra-hepatic tissues. Hypomethylated (c and d) forms of T3 show the highest in vitro and in vivo metabolism and are also the most potent natural xenobiotics of the entire vitamin E family of compounds. These stimulate a stress response with the induction of detoxification and antioxidant genes. Depending on the intensity of this response, these genes may confer cell protection or alternatively they stimulate a senescence-like phenotype with cell cycle inhibition or even mitochondrial toxicity and apoptosis. In cancer cells, the uptake rate and thus the cell content of these vitamers is again higher for the hypomethylated forms, and it is the critical factor that drives the dichotomy between protection and toxicity responses to different T3 forms and doses. These aspects suggest the potential for marked biological activity of hypomethylated ''highly metabolized'' T3 that may result in cytoprotection and cancer prevention or even chemotherapeutic effects. Cytotoxicity and metabolism of hypomethylated T3 have been extensively investigated in vitro using different cell model systems that will be discussed in this review paper as regard molecular mechanisms and possible relevance in cancer therapy.Keywords Tocotrienols Á Vitamin E Á Breast cancer Á Antioxidants Á Apoptosis Á Cell signaling Á Inflammation Á Metabolism Á Gene expression Á Cell redox T3 structure-function and specificity of actionIn the vitamin E family of molecules, tocotrienols (T3) are often considered of minor importance since these are less abundant than a and c tocopherol (TOH) in the circulation and in solid tissues. This has contributed to hinder our knowledge on the biological functions of this group of vitamers that is now regaining great interest, thanks to a number of recent studies that suggested health-promoting functions related with the cholesterol-lowering, cytoprotective, and anticarcinogenic effects of T3 [reviewed in (Aggarwal et al. (2010)].Structure-function studies demonstrate that many of these functions are more potent when the unsaturated (isoprenyl) side chain of T3 is combined with a hypomethylated (HM) chroman ring. The unsaturated chain characteristic of all the T3 forms confers well-defined physical and chemical characteristics that appear to include vitamer-specific interactions with other lipids and cell proteins (Atkinson

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“…Although most of the tocopherols and tocotrienols have similar in vitro antioxidant activity (Zingg and Azzi 2004), a-tocopherol is acknowledged as being the most biologically active E vitamer (Hosomi et al 1997). Of the eight possible stereoisomers of atocopherol, RRR-a-tocopherol has the greatest potency in vivo (Burton et al 1998;Brigelius-Flohé and Traber 1999).…”

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confidence: 99%

Influence of Stress and Dietary Natural‐Source Vitamin E on Nonspecific Immunocompetence, Tissue Tocopherol Composition, and Postslaughter Fillet Oxidative Stability in Sunshine Bass

Trushenski

Kohler

2007

N American J Aquac

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We evaluated the effects of stressor exposure and super‐requirement levels of RRR‐α‐tocopheryl acetate (natural‐source vitamin E [NSVE]) on production performance and nonspecific immunocompetency of juvenile sunshine bass (female white bass Morone chrysops × male striped bass M. saxatilis). Stressor exposure elicited physiological changes consistent with the generalized stress response, and the magnitude of responses generally mirrored stressor severity. Stressor exposure resulted in lower fillet peroxides and greater aldehydes after short‐term frozen storage, whereas increasing dietary NSVE was associated with a nonsignificant reduction in aldehydes after long‐term storage. Fillet α‐tocopherol content increased linearly with dietary NSVE, exceeding reported tissue levels achieved with synthetic vitamin E (SYNE). Although we observed no significant immunological effects of stress or dietary NSVE content, sampling time and high individual‐to‐individual variation probably restricted our ability to resolve statistical significance. Similar results of vitamin E supplementation have previously been reported; however, the effective dietary concentrations we observed for NSVE are low in comparison with values reported for SYNE. The potential of RRR‐α‐tocopheryl acetate as a highly active vitamin E source for aquaculture feeds warrants further evaluation of the relative suitability of NSVE in meeting the demands of optimal aquaculture nutrition.

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Affinity for α‐tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs

Cited by 584 publications

References 18 publications

Effects of oral micellized natural vitamin E (d-α-tocopherol) v. synthetic vitamin E (dl-α-tocopherol) in feed on α-tocopherol levels, stereoisomer distribution, oxidative stress and the immune response in piglets

Effects of oral micellized natural vitamin E (d-α-tocopherol) v. synthetic vitamin E (dl-α-tocopherol) in feed on α-tocopherol levels, stereoisomer distribution, oxidative stress and the immune response in piglets

Why tocotrienols work better: insights into the in vitro anti-cancer mechanism of vitamin E

Influence of Stress and Dietary Natural‐Source Vitamin E on Nonspecific Immunocompetence, Tissue Tocopherol Composition, and Postslaughter Fillet Oxidative Stability in Sunshine Bass

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