Monthly Archives: May 2016

Analytical strategies to assess the functional metabolome of vitamin E.

Torquato P, Ripa O, Giusepponi D, Galarini R, Bartolini D, Wallert M, Pellegrino R, Cruciani G, Lorkowski S, Birringer M, Mazzini F, Galli F.

J Pharm Biomed Anal. 2016 May 30;124:399-412. doi: 10.1016/j.jpba.2016.01.056. Review.

Abstract

After more than 90 years from its discovery and thousands of papers published, the physiological roles of vitamin E (tocopherols and tocotrienols) are still not fully clarified. In the last few decades, the enzymatic metabolism of this vitamin has represented a stimulating subject of research. Its elucidation has opened up new horizons to the interpretation of the biological function of that class of molecules. The identification of specific properties for some of the physiological metabolites and the definition of advanced analytical techniques to assess the human metabolome of this vitamin in vivo, have paved the way to a series of hypotheses on the functional implications that this metabolism may have far beyond its catabolic role. The present review collects the available information on the most relevant analytical strategies employed to assess the status and metabolism of vitamin E in humans as well as in other model systems. A particular focus is dedicated to the analytical methods used to measure vitamin E metabolites, and particularly long-chain metabolites, in biological fluids and tissues. Preliminary information on a new LC-APCI-MS/MS method to measure these metabolites in human serum is reported.

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Synergistic cytotoxic effects of combined δ-tocotrienol and jerantinine B on human brain and colon cancers.

Abubakar IB, Lim KH, Kam TS, Loh HS.

J Ethnopharmacol. 2016 May 26;184:107-18. doi: 10.1016/j.jep.2016.03.004.

Abstract

The genus Tabernaemontana has widespread distribution throughout tropical and subtropical parts of the world, i.e. Africa, Asia and America which has long been used for treatments of different disease conditions including tumours, wounds, syphilis, stomach ache and headache. Some Tabernaemontana species are used for treatment of piles, spleen and abdominal tumours in India. In particular, the leaf of Tabernaemontana corymbosa is used for treatment of tumours in Bangladesh. Parts of the plant or whole plants are used as decoctions, steam bath, powder and ointments. The present study was undertaken to study the mechanism of apoptosis induction in human glioblastoma (U87MG) and colorectal adenocarcinoma (HT-29) cancer cells by a novel indole alkaloid, jerantinine B isolated from T. corymbosa, δ-tocotrienoland the combined low-dose treatments of δ-tocotrienol with IC20 dose of jerantinine B. In summary, this study demonstrated the mechanism for cytotoxic potency of δ-tocotrienol and jerantinine B against U87MG and HT-29 cells. Furthermore, combined low-dose treatments induced concurrent synergistic inhibition of cancer cell growth with concomitant dose reduction thus minimizing toxicity to normal cells and improving potency of δ-tocotrienol and jerantinine B.

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A pill for Parkinson’s?

The National Neuroscience Institute (NNI) is testing the substance, which is currently already available in a pill form. NNI signed a Memorandum of Understanding (MOU) with Malaysian pharmaceutical company Hovid Berhad to test whether palm tocotrienol – extracted from crude palm oil – works in experimental models of Parkinson’s disease. Clinical studies will be carried out subsequently.
“Our short- to mid-term plan is to come up with a drug to delay the onset of Parkinson’s for those at risk of the disease,” said Professor Tan Eng King, NNI’s Director of Research.

Circulating Alpha-Tocopherol and Insulin Sensitivity Among Older Men With Chronic Kidney Disease.

Xu H, Xiong Z, Ärnlöv J, Qureshi AR, Cederholm T, Sjögren P, Lindholm B, Risérus U, Carrero JJ.

J Ren Nutr. 2016 May;26(3):177-82. doi: 10.1053/j.jrn.2015.11.005.

Abstract

Insulin resistance is common in individuals with chronic kidney disease (CKD) and may be partly explained by modifiable risk factors. In the general population, vitamin E supplementation has been suggested to improve both insulin sensitivity and secretion. We here explore the potential role of vitamin E as a modifiable risk factor for insulin resistance among individuals with CKD. A total of 273 nondiabetic men aged 70 to 71 years with CKD defined as either cystatin C estimated glomerular filtration rate < 60 mL/minute/1.73 m(2) or urinary albumin excretion rate ≥ 20 μg/minute were included in this study. Serum α-, β-, and γ-tocopherol concentrations were measured by high-performance liquid chromatography and expressed as μmol/total serum cholesterol and triglycerides (in mmol). Dietary vitamin E intake was estimated from 7-day food records. Insulin sensitivity index (M/I ratio) was measured by hyperinsulinemic-euglycemic glucose clamps. Univariate and multivariate regression models were fitted to assess the association between M/I and circulating concentrations of tocopherols. Conclusion, serum α-tocopherol concentration associates with insulin sensitivity in nondiabetic older men with CKD.

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Supplementation of culture media with vitamin E improves mouse antral follicle maturation and embryo development from vitrified ovarian tissue.

Farzollahi M, Tayefi-Nasrabadi H, Mohammadnejad D, Abedelahi A.

J Obstet Gynaecol Res. 2016 May;42(5):526-35. doi: 10.1111/jog.12933.

Abstract

The aim of this study was to evaluate the effects of preventive vitamin E (α-tocopherol) on antral follicle development and embryogenesis of oocytes obtained after vitrification of mouse ovarian tissue. Female Balb/c mice were killed by cervical dislocation after the injection of pregnant mare’s serum gonadotrophin (10 IU) and their ovaries were randomly divided into three groups: control or non-vitrified (n = 10), vitrification 1 (5, 10% ethylene glycol + 5, 10% dimethylsulfoxide) (n = 15), and vitrification 2 (10, 15% ethylene glycol + 10, 15% dimethylsulfoxide) (n = 15) with ascending concentration of cryoprotectants. After toxicity tests and vitrification-warming, mechanically isolated antral follicles were cultured in α-minimum essential medium, which was supplemented with or without α-tocopherol (100 μM). The follicular maturation rates and embryo development were collected and assessed. Also, the viability, morphology and ultrastructure of derived antral follicles from vitrified ovaries were analyzed. Results showed the morphology and ultrastructure of follicles were well preserved in the vitrified groups and α-tocopherol supplementation of culture media significantly increased the proportion of oocytes that reached metaphase II blastocyst rates compared to non-α-tocopherol supplemented media (P < 0.01). In conclusion, Vitamin E improves in vitro maturation rates and blastocyst rates of oocytes that are isolated from vitrified ovarian tissue.

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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.

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The influence of droplet size on the stability, in vivo digestion, and oral bioavailability of vitamin E emulsions.

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.

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δ- and γ-tocopherols inhibit phIP/DSS-induced colon carcinogenesis by protection against early cellular and DNA damages.

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.

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Dehydroepiandrosterone alters vitamin E status and prevents lipid peroxidation in vitamin E-deficient rats.

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.

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Alpha-tocopherol ameliorates experimental autoimmune encephalomyelitis through the regulation of Th1 cells.

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.

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