A Comparison of Natural (D-α-tocopherol) and Synthetic (DL-α-tocopherol Acetate) Vitamin E Supplementation on the Growth Performance, Meat Quality and Oxidative Status of Broilers.

Cheng K, Niu Y, Zheng XC, Zhang H, Chen YP, Zhang M, Huang XX, Zhang LL, Zhou YM, Wang T.

Asian-Australas J Anim Sci. 2016 May;29(5):681-8. doi: 10.5713/ajas.15.0819.

Abstract

The present study was conducted to compare the supplementation of natural (D-α-tocopherol) and synthetic (DL-α-tocopherolacetate) vitamin E on the growth performance, meat quality, muscular antioxidant capacity and genes expression related to oxidative status of broilers. A total of 144 1 day-old Arbor Acres broiler chicks were randomly allocated into 3 groups with 6 replicates of 8 birds each. Birds were given a basal diet (control group), and basal diet supplemented with either 20 IU D-α-tocopherol or DL-α-tocopherolacetate for 42 days, respectively. The results indicated that treatments did not alter growth performance of broilers (p>0.05). Compared with the control group, concentration of α-tocopherol in the breast muscle was increased by the supplementation of vitamin E (p<0.05). In the thigh, α-tocopherol content was also enhanced by vitamin E inclusion, and this effect was more pronounced in the natural vitamin E group (p<0.05). Vitamin E supplementation increased the redness of breast (p<0.05). In the contrast, the inclusion of synthetic vitamin E decreased lightness of thigh (p<0.05). Dietary vitamin E inclusion reduced drip loss at 24 h of thigh muscle (p<0.05), and this effect was maintained for drip loss at 48 h in the natural vitamin E group (p<0.05). Broilers given diet supplemented with vitamin E showed decreased malondialdehyde (MDA) content in the breast (p<0.05). Additionally, natural rather than synthetic vitamin E reduced MDA accumulation in the thigh (p<0.05). Neither natural nor synthetic vitamin E supplementation altered muscular mRNA abundance of genes related to oxidative stress (p>0.05). It was concluded that vitamin E supplementation, especially the natural vitamin E, can enhance the retention of muscular α-tocopherol, improve meat quality and muscular antioxidant capacity of broilers.

Parthasarathi S, Muthukumar SP, Anandharamakrishnan C.

Food Funct. 2016 May 18;7(5):2294-302. doi: 10.1039/c5fo01517k.

Abstract

Vitamin E (α-tocopherol) is a nutraceutical compound, which has been shown to possess potent antioxidant and anticancer activity. However, its biological activity may be limited by its poor bioavailability. Colloidal delivery systems have shown wide applications in the food and pharmaceutical industries to deliver lipophilic bioactive compounds. In this study, we have developed conventional and nanoemulsions of vitamin E from food grade ingredients (sunflower oil, saponin, and water) and showed the nanoemulsion formulation increased the oral bioavailability when compared to the conventional emulsion. The mean droplet diameters in the nano and conventional emulsions were 0.277 and 1.285 μm, respectively. The stability of the emulsion formulation after thermal processing, long-term storage at different temperatures, mechanical stress and in plasma was determined. The results showed that the saponin coated nanoemulsion was stable to droplet coalescence during thermal processing (30-90 °C), long-term storage and mechanical stress when compared to the conventional emulsion. The biological fate of the emulsion formulations were studied using male Wistar rats as an animal model. The emulsion droplet stability during passage through the gastrointestinal tract was evaluated by their introduction into rat stomachs. Microscopy was used to investigate the structural changes that occurred during digestion. Both the conventional emulsion and nanoemulsion formulations showed strong evidence of droplet flocculation and coalescence during in vivo digestion. The in vivo oral bioavailability study revealed that vitamin E in a nanoemulsion form showed a 3-fold increase in the AUC when compared to the conventional emulsion. The information reported in this study will facilitate the design of colloidal delivery systems using nanoemulsion formulations.

Chen JX, Liu A, Lee MJ, Wang H, Yu S, Chi E, Reuhl K, Suh N, Yang CS.

Mol Carcinog. 2016 May 13. doi: 10.1002/mc.22481. [Epub ahead of print]

Abstract

Tocopherols, the major forms of vitamin E, are a family of fat-soluble compounds that exist in alpha (α-T), beta (β-T), gamma (γ-T), and delta (δ-T) variants. A cancer preventive effect of vitamin E is suggested by epidemiological studies. However, past animal studies and human intervention trials with α-T, the most active vitamin E form, have yielded disappointing results. A possible explanation is that the cancer preventive activity of α-T is weak compared to other tocopherol forms. In the present study, we investigated the effects of δ-T, γ-T, and α-T (0.2% in diet) in a novel colon cancer model induced by the meat-derived dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS)-induced colitis in CYP1A-humanized (hCYP1A) mice. PhIP/DSS treatments induced multiple polypoid tumors, mainly tubular adenocarcinomas, in the middle to distal colon of the hCYP1A mice after 10 wk. Dietary supplementation with δ-T and γ-T significantly reduced colon tumor formation and suppressed markers of oxidative and nitrosative stress (i.e., 8-oxo-dG and nitrotyrosine) as well as pro-inflammatory mediators (i.e., NF-κB p65 and p-STAT3) in tumors and adjacent tissues. By administering δ-T at different time periods, we obtained results suggesting that the inhibitory effect of δ-T against colon carcinogenesis is mainly due to protection against early cellular and DNA damages caused by PhIP. α-T was found to be ineffective in inhibiting colon tumors and less effective in attenuating the molecular changes. Altogether, we demonstrated strong cancer preventive effects of δ-T and γ-T in a physiologically relevant model of human colon cancer.

Miyazaki H, Takitani K, Koh M, Inoue A, Tamai H.

J Clin Biochem Nutr. 2016 May;58(3):223-31. doi: 10.3164/jcbn.15-133.

Abstract

In humans, dehydroepiandrosterone and its sulfate ester metabolite DHEA-S are secreted predominantly from the adrenal cortex, and dehydroepiandrosterone is converted to steroid hormones, including androgens and estrogens, and neurosteroid. Dehydroepiandrosterone exerts protective effects against several pathological conditions. Although there are reports on the association between dehydroepiandrosterone and vitamins, the exact relationship between dehydroepiandrosterone and vitamin Eremains to be determined. Therefore, we attempted to elucidate the effect of dehydroepiandrosterone on vitamin E status and the expression of various vitamin E-related proteins, including binding proteins, transporters, and cytochrome P450, in vitamin E-deficient rats. Plasma α-tocopherol levels in vitamin E-deficient rats increased in response to dehydroepiandrosterone administration. The expression of hepatic α-tocopherol transfer protein was repressed in vitamin E-deficient rats compared to that in control rats; however, dehydroepiandrosterone administration significantly upregulated this expression. Hepatic expression of CYP4F2, an α-tocopherolmetabolizing enzyme, in vitamin E-deficient rats was decreased by dehydroepiandrosterone administration, whereas hepatic expression of ATP-binding cassette transporter A1, an α-tocopherol transporter, was not altered following dehydroepiandrosterone administration. Dehydroepiandrosterone repressed lipid peroxidation in the liver of vitamin E-deficient rats. Therefore, adequate dehydroepiandrosterone supplementation may improve lipid peroxidation under several pathological conditions, and dehydroepiandrosterone may modulate α-tocopherol levels through altered expression of vitamin E-related proteins.

Xue H, Ren H, Zhang L, Sun X, Wang W, Zhang S, Zhao J, Ming L.

Iran J Basic Med Sci. 2016 May;19(5):561-6.

Abstract

Multiple sclerosis (MS) is a serious neurological autoimmune disease, it commonly affects young adults. Vitamin E (Vit E) is an important component of human diet with antioxidant activity, which protects the body’s biological systems. In order to assess the effect of Vit E treatment on this autoimmune disease, we established experimental autoimmune encephalomyelitis (EAE), the animal model of MS, and treated EAE with α-tocopherol (AT) which is the main content of Vit E. Results show that AT was able to attenuate the severity of EAE and delay the disease progression. H&E staining and fast blue staining indicated that AT reduced the inflammation and the demyelination reaction in the spinal cord. Treatment with AT significantly decreased the proliferation of splenocytes. AT also inhibited the production of IFN-γ (Th1 cytokine), though the other cytokines were only affected slightly. According to the results, AT ameliorated EAE, through suppressing the proliferation of T cells and the Th1 response. AT may be used as a potential treatment for MS.

Xiong A, Yu W, Liu Y, Sanders BG, Kline K.

Mol Carcinog. 2016 May;55(5):420-30. doi: 10.1002/mc.22291.

Abstract

Study investigated the ability of docosahexaenoic acid (DHA) alone and in combination with gamma-tocotrienol (γT3) to eliminate aldehyde dehydrogenase positive (ALDH+) cells and to inhibit mammosphere formation, biomarker and functional assay for tumor initiating cells (TICs), respectively, in human triple negative breast cancer cells (TNBCs), and investigated possible mechanisms of action. DHA upregulated Src homology region 2 domain-containing protein tyrosine phosphatase-1 (SHP-1) protein levels and suppressed levels of phosphorylated signal transducer and activator of transcription-3 (pStat3) and its downstream mediators c-Myc, and cyclin D1. siRNA to SHP-1 enhanced the percentage of ALDH+ cells and Stat-3 signaling, as well as inhibited, in part, the ability of DHA to reduce the percentage of ALDH+ cells and Stat-3 signaling. γT3 alone and in combination with DHA reduced ALDH+ TNBCs, up-regulated SHP-1 protein levels, and suppressed Stat-3 signaling. Taken together, data demonstrate the anti-TIC potential of achievable concentrations of DHA alone as well as in combination with γT3.

Ghosh SP, Pathak R, Kumar P, Biswas S, Bhattacharyya S, Kumar VP, Hauer-Jensen M, Biswas R.

Radiat Res. 2016 May;185(5):485-95. doi: 10.1667/RR14248.1.

Abstract

Ionizing radiation causes depletion of hematopoietic cells and enhances the risk of developing secondary hematopoietic malignancies. Vitamin E analog gamma-tocotrienol (GT3), which has anticancer properties, promotes postirradiation hematopoietic cell recovery by enhancing spleen colony-forming capacity, and provides protection against radiation-induced lethality in mice. However, the underlying molecular mechanism involved in GT3-mediated postirradiation survival is not clearly understood. Recent studies have shown that natural dietary products including vitamin E provide a benefit to biological systems by modulating microRNA (miR) expression. In this study, we show that GT3 differentially modulates the miR footprint in the spleen of irradiated mice compared to controls at early times (day 1), as well as later times (day 4 and 15) after total-body irradiation. We observed that miR expression was altered in a dose- and time-dependent manner in GT3-pretreated spleen tissues from total-body irradiated mice. GT3 appeared to affect the expression of a number of radiation-modulated miRs known to be involved in hematopoiesis and lymphogenesis. Moreover, GT3 pretreatment also suppressed the upregulation of radiation-induced p53, suggesting the function of GT3 in the prevention of radiation-induced damage to the spleen. In addition, we have shown that GT3 significantly reduced serum levels of Flt3L, a biomarker of radiation-induced bone marrow aplasia. Further in silico analyses of the effect of GT3 implied the association of p38 MAPK, ERK and insulin signaling pathways. Our study provides initial insight into the mechanism by which GT3 mediates protection of spleen after total-body irradiation.

Xia W, Mo H.

J Nutr Biochem. 2016 May;31:1-9. doi: 10.1016/j.jnutbio.2015.10.011. Review.

Abstract

Currently there is no cure for Alzheimer’s disease (AD); clinical trials are underway to reduce amyloid generation and deposition, a neuropathological hallmark in brains of AD patients. While genetic factors and neuroinflammation contribute significantly to AD pathogenesis, whether increased cholesterol level is a causative factor or a result of AD is equivocal. Prenylation of proteins regulating neuronal functions requires mevalonate-derived farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). The observation that the levels of FPP and GGPP, but not that of cholesterol, are elevated in AD patients is consistent with the finding that statins, competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, reduce FPP and GGPP levels and amyloid β protein production in preclinical studies. Retrospective studies show inverse correlations between incidence of AD and the intake and serum levels of the HMG CoA reductase-suppressive tocotrienols; tocopherols show mixed results. Tocotrienols, but not tocopherols, block the processing and nuclear localization of sterol regulatory element binding protein-2, the transcriptional factor for HMG CoA reductase and FPP synthase, and enhance the degradation of HMG CoA reductase. Consequently, tocotrienols deplete the pool of FPP and GGPP and potentially blunt prenylation-dependent AD pathogenesis. The antiinflammatory activity of tocotrienolsfurther contributes to their protection against AD. The mevalonate- and inflammation-suppressive activities of tocotrienols may represent those of an estimated 23,000 mevalonate-derived plant secondary metabolites called isoprenoids, many of which are neuroprotective. Tocotrienol-containing plant foods and tocotrienol derivatives and formulations with enhanced bioavailability may offer a novel approach in AD prevention and treatment.

Tan JK, Then SM, Mazlan M, Raja Abdul Rahman RN, Jamal R, Wan Ngah WZ.

J Nutr Biochem. 2016 May;31:28-37. doi: 10.1016/j.jnutbio.2015.12.019.

Abstract

Bcl-2 family proteins are crucial regulators of apoptosis. Both pro- and antiapoptotic members exist, and overexpression of the latter facilitates evasion of apoptosis in many cancer types. Bcl-2 homology domain 3 (BH3) mimetics are small molecule inhibitors of antiapoptotic Bcl-2 family members, and these inhibitors are promising anticancer agents. In this study, we report that gamma-tocotrienol (γT3), an isomer of vitamin E, can inhibit Bcl-2 to induce apoptosis. We demonstrate that γT3 induces cell death in human neuroblastoma SH-SY5Y cells by depolarising the mitochondrial membrane potential, enabling release of cytochrome c to the cytosol and increasing the activities of caspases-9 and -3. Treatment of cells with inhibitors of Bax or caspase-9 attenuated the cell death induced by γT3. Simulated docking analysis suggested that γT3 binds at the hydrophobic groove of Bcl-2, while a binding assay showed that γT3 competed with a fluorescent probe to bind at the hydrophobic groove. Our data suggest that γT3 mimics the action of BH3-only protein by binding to the hydrophobic groove of Bcl-2 and inducing apoptosis via the intrinsic pathway in a Bax- and caspase-9-dependent manner.

Yamashita S, Baba K, Makio A, Kumazoe M, Huang Y, Lin IC, Bae J, Murata M, Yamada S, Tachibana H.

Biochem Biophys Res Commun. 2016 May 13;473(4):801-7. doi: 10.1016/j.bbrc.2016.03.111.

Abstract

Previous studies have identified biomolecules that mediate the physiological actions of food factors, such as amino acids, vitamins, fatty acids, minerals, plant polyphenols, and lactobacilli, suggesting that our bodies are equipped with an innate system that senses which food factors are required to maintain our health. However, the effects of environmental factors on food factor sensing (FFS) remains largely unknown. Tocotorienols (T3s), which belongs to the vitamin E family, possess several physiological functions, including cholesterol lowering and neuroprotective effects. Here, we investigated the effects of naturally abundant γ-T3 on FFS-related gene expressions in melanoma using a DNA chip. Our results showed that γ-T3 increased the expression level of aryl hydrocarbon receptor (AhR), a sensing molecule to plant polyphenol baicalein. The co-treatment with γ-T3 and baicalein enhanced the anti-proliferative activity of baicalein, accompanied by the downstream events of AhR-activation induced by baicalein. These data suggest that γ-T3 upregulates AhR expression and enhances its sensitivity to baicalein.]