Monthly Archives: August 2016

Effects of Tocotrienols on Insulin Secretion-Associated Genes Expression of Rat Pancreatic Islets in a Dynamic Culture.

Chia LL, Jantan I, Chua KH, Lam KW, Rullah K, Aluwi MF.

Front Pharmacol. 2016 Aug 30;7:291. doi: 10.3389/fphar.2016.00291.

Abstract

Tocotrienols (T3) are well-known for their antioxidant properties besides showing therapeutic potential in clinical complications such as hyperlipidemia induced by diabetes. The aim of this study was to determine the effects of δ-T3, γ-T3, and α-T3 on insulin secretion-associated genes expression of rat pancreatic islets in a dynamic culture. Pancreatic islets freshly isolated from male Wistar rats were treated with T3 for 1 h at 37°C in a microfluidic system with continuous operation. The cells were collected for total RNA extraction and reverse-transcribed, followed by measurement of insulin secretion-associated genes expression using quantitative real-time polymerase chain reaction. Molecular docking experiments were performed to gain insights on how the T3 bind to the receptors. Short-term exposure of δ- and γ-T3 to pancreatic β cells in a stimulant glucose condition (16.7 mM) significantly regulated preproinsulin mRNA levels and insulin gene transcription. In contrast, α-T3 possessed less ability in the activation of insulin synthesis level. Essentially, potassium chloride (KCl), a β cell membrane depolarising agent added into the treatment further enhanced the insulin production. δ- and γ-T3 revealed significantly higher quantitative expression in most of the insulin secretion-associated genes groups containing 16.7 mM glucose alone and 16.7 mM glucose with 30 mM KCl ranging from 600 to 1200 μM (p < 0.05). The findings suggest the potential of δ-T3 in regulating insulin synthesis and glucose-stimulated insulin secretion through triggering pathway especially in the presence of KCl.

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Vitamin E and the risk of childhood asthma.

Strait RT, Camargo CA.

Expert Rev Respir Med. 2016 Aug;10(8):881-90. doi: 10.1080/17476348.2016.1184090.

Abstract

Asthma, a heterogeneous disease with multiple phenotypes, remains a significant health problem. Present treatments are not curative and prevention should be our ultimate goal. Vitamin E supplementation presents a potential easy and cheap preventive therapy but the results of studies are confusing and sometimes contradictory. Clarification is needed.Animal studies and research in pregnant women suggest enhanced lifetime resistance to asthma with appropriate fetal exposure to vitamin E. Vitamin E‘s preventive role is complex and includes functional variations of the different isoforms. Expert commentary: We review the most recent literature on the role of vitamin E isoforms on: lung inflammation, immune development, animal and clinical studies during pregnancy, and the potential influence of vitamin E isoforms on asthma development in offspring. We point out where data are seemingly contradictory, explain why this is so, and comment on where further clarifying research is needed and its future direction.

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Vitamin E and Phosphoinositides Regulate the Intracellular Localization of the Hepatic α-Tocopherol Transfer Protein.

Chung S, Ghelfi M, Atkinson J, Parker R, Qian J, Carlin C, Manor D.

J Biol Chem. 2016 Aug 12;291(33):17028-39. doi: 10.1074/jbc.M116.734210.

Abstract

α-Tocopherol (vitamin E) is an essential nutrient for all vertebrates. From the eight naturally occurring members of the vitamin E family, α-tocopherol is the most biologically active species and is selectively retained in tissues. The hepatic α-tocopherol transfer protein (TTP) preferentially selects dietary α-tocopherol and facilitates its transport through the hepatocyte and its secretion to the circulation. In doing so, TTP regulates body-wide levels of α-tocopherol. The mechanisms by which TTP facilitates α-tocopherol trafficking in hepatocytes are poorly understood. We found that the intracellular localization of TTP in hepatocytes is dynamic and responds to the presence of α-tocopherol. In the absence of the vitamin, TTP is localized to perinuclear vesicles that harbor CD71, transferrin, and Rab8, markers of the recycling endosomes. Upon treatment with α-tocopherol, TTP- and α-tocopherol-containing vesicles translocate to the plasma membrane, prior to secretion of the vitamin to the exterior of the cells. The change in TTP localization is specific to α-tocopherol and is time- and dose-dependent. The aberrant intracellular localization patterns of lipid binding-defective TTP mutants highlight the importance of protein-lipid interaction in the transport of α-tocopherol. These findings provide the basis for a proposed mechanistic model that describes TTP-facilitated trafficking of α-tocopherol through hepatocytes.

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Establishment of reference values of α-tocopherol in plasma, red blood cells and adipose tissue in healthy children to improve the management of chylomicron retention disease, a rare genetic hypocholesterolemia.

Cuerq C, Restier L, Drai J, Blond E, Roux A, Charriere S, Michalski MC, Di Filippo M, Levy E, Lachaux A, Peretti N.

Orphanet J Rare Dis. 2016 Aug 12;11(1):114. doi: 10.1186/s13023-016-0498-8.

Abstract

Chylomicron retention disease (CMRD), a rare genetic hypocholesterolemia, results in neuro-ophtalmologic damages, which can be prevented by high doses of vitamin E during infancy. In these patients, plasma vitamin E concentration is significantly reduced due to defects of chylomicron secretion. Vitamin E in adipose tissue (AT) and red blood cells (RBC) have been proposed as potential relevant biomarkers of vitamin E status but no reference values in children are available. The objectives were (i) to establish age-reference intervals in healthy children for α-tocopherol in plasma, red blood cells (RBC) and adipose tissue (AT) and (ii) to determine the variations of α-tocopherol in patients with CMRD after oral treatment with vitamin E. Summary, this study establishes pediatric reference intervals for α-tocopherol in plasma, RBC and AT. These values will be beneficial in assessing accurate α-tocopherol status in children and to optimize the monitoring of rare diseases such as CMRD. Our data suggest that RBC α-tocopherol, appears as a relevant biomarker to appreciate the effectiveness of treatment with α-tocopherol in patients with a rare primary hypocholesterolemia. The biopsy of AT could be used at diagnosis to assess the severity of the vitamin Edeficiency and periodically after a long duration of vitamin E therapy to assess whether the treatment is effective, based on reference intervals defined in this study.

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γ-Tocotrienol reversal of epithelial-to-mesenchymal transition in human breast cancer cells is associated with inhibition of canonical Wnt signalling.

Ahmed RA, Alawin OA, Sylvester PW.

Cell Prolif. 2016 Aug;49(4):460-70. doi: 10.1111/cpr.12270.

Abstract

Frizzled-7 (FZD7) receptor-dependent activation of the canonical Wnt/β-catenin pathway plays a crucial role in epithelial-to-mesenchymal transition (EMT) and breast cancer metastasis. FZD7 and its co-receptor, low-density lipoprotein receptor-related protein 6 (LRP6), are highly expressed in MDA-MB-231 and T-47D breast cancer cells, and endogenous ligands for FZD7 include Wnt3a and Wnt5a/b. γ-Tocotrienol, a natural isoform of vitamin E, inhibits human breast cancer cell proliferation and EMT. Here, studies have been conducted to investigate the role of the canonical Wnt pathway in mediating inhibitory effects of γ-tocotrienolon EMT in human breast cancer cells. Results show γ-Tocotrienol was found to induce dose-responsive inhibition of MDA-MB-231 and T-47D cell growth at doses that had no effect on immortalized normal MCF-10A mammary epithelial cells. These growth inhibitory effects were associated with suppression in canonical Wnt signalling, reversal of EMT and significant reduction in breast cancer cell motility. In conclusion, γ-Tocotrienol suppression of metastatic breast cancer cell proliferation and EMT was associated with suppression of the canonical Wnt/β-catenin signalling pathway.

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The potentiation of the radioprotective efficacy of two medical countermeasures, gamma-tocotrienol and amifostine, by a combination prophylactic modality.

Singh VK, Fatanmi OO, Wise SY, Newman VL, Romaine PL, Seed TM.

Radiat Prot Dosimetry. 2016 Aug 19. [Epub ahead of print]

Abstract

This study was designed to evaluate the possible potentiation of survival protection afforded by relatively low-dose amifostine prophylaxis against total body irradiation in combination with a protective, less toxic agent, gamma-tocotrienol (GT3). Mice were administered amifostine and/or GT3, then exposed to 9.2 Gy 60Co γ-irradiation and monitored for survival for 30 days. To investigate cytokine stimulation, mice were administered amifostine or GT3; serum samples were collected and analyzed for cytokines. Survival studies show single treatments of GT3 or amifostine significantly improved survival, compared to the vehicle, and combination treatments resulted in significantly higher survival compared to single treatments. In vivo studies with GT3 confirmed prior work indicating GT3 induces granulocyte colony-stimulating factor (G-CSF). This approach, the prophylactic combination of amifostine and GT3, which act through different mechanisms, shows promise and should be investigated further as a potential countermeasure for acute radiation syndrome.

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Study Finds Improved Endurance from Whey and Palm Tocotrienol Combo

“We were surprised by the benefit of tocotrienols and whey protein isolate, and when our data combines with that of prior research, the benefits on exercise endurance are quite compelling, said Andrew Betik, lead author and  postdoctoral researcher for the Colleges of Health & Biomedicine and Sport & Exercise Science at Victoria University. “The mechanisms of this will be very interesting to elucidate.”

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Vitamin E Deficiency Is Rampant — Why You Don’t Want to Be

Vitamin E is an important fat-soluble vitamin and antioxidant that helps combat damaging free radicals. It also plays a role in the making of red blood cells and helps your body use vitamin K, the latter of which is important for heart health.

Unfortunately, estimates suggest about 6 billion people worldwide are deficient in this basic micronutrient.

According to a recent review presented at the World Congress of Public Health Nutrition, more than 90 percent of Americans fail to reach the recommended daily allowance (RDA) of vitamin E.

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Natural Immunity Boost

Vitamin E has long been known to be an antioxidant, capable of destroying potentially harmful free radicals in our body. There are 2 main types of vitamin E: tocopherols and tocotrienols. To date, tocopherols have been extensively researched, and nearly all the vitamin E supplements available today are derived from tocopherols. Tocotrienols, compared to tocopherols, are only starting to receive more attention from researchers, but even at this early stage, research is uncovering a considerable amount of potential benefits.

HealthToday sits down with Professor Ammu Radhakrishnan, who shares with us a study, in which she was involved, that demonstrates the potential benefits of tocotrienols to our body’s defense against infections.

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Progenitor Cell Mobilization by Gamma-tocotrienol: A Promising Radiation Countermeasure.

Singh VK, Fatanmi OO, Verma A, Newman VL, Wise SY, Romaine PL, Berg AN.

Health Phys. 2016 Aug;111(2):85-92. doi: 10.1097/HP.0000000000000458.

Abstract

This article reviews studies of progenitor mobilization with gamma-tocotrienol (GT3), a tocol under advanced development as a radiation countermeasure for acute radiation syndrome (ARS). GT3 protects mice against high doses of ionizing radiation and induces high levels of granulocyte colony-stimulating factor (G-CSF). GT3-induced G-CSF in conjunction with AMD3100 (a chemokine receptor antagonist clinically used to improve the yield of mobilized progenitors) mobilizes progenitors; these mobilized progenitors mitigate injury when infused to mice exposed to acute, high-dose ionizing radiation. The administration of a G-CSF antibody to GT3-injected donor mice abrogated the radiomitigative efficacy of blood or peripheral blood mononuclear cells (PBMC) in irradiated recipient mice. The efficacy of GT3-injected donor mice blood or PBMC was comparable to a recently published article involving blood or mononuclear cells obtained from mice injected with G-CSF. The injected progenitors were found to localize in various tissues of irradiated hosts. The authors demonstrate the efficacy of a bridging therapy in a preclinical animal model that allows the lymphohematopoietic system of severely immunocompromised mice to recover. This suggests that GT3 is a highly effective agent for radioprotection and mobilizing progenitors with significant therapeutic potential. Therefore, GT3 may be considered for further translational development and ultimately for use in humans.

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