Utilization of Vitamin E Analogs to Protect Normal Tissues While Enhancing Antitumor Effects

Aykin-Burns N, Pathak R, Boerma M, Kim T, Hauer-Jensen M

Semin Radiat Oncol. 2019 Jan;29(1):55-61. doi: 10.1016/j.semradonc.2018.10.008.

Abstract

Despite advances in radiation delivery techniques, side effects of radiation therapy due to radiation exposure of normal tissues are common and can limit the deliverable dose to tumors. Significant interests lie in pharmacologic modifiers that may protect against normal tissue toxicity from cancer treatment while simultaneously enhancing the tumor response to therapy. While no such treatments are available in the clinic, this is an area of active preclinical and clinical research. This review summarizes research studies that provide evidence to indicate that tocotrienols, natural forms of vitamin E, are potent radiation protectors and may also have antitumor effects. Hence, several current clinical trials test tocotrienols as concomitant treatment in cancer therapies.

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Effects of alpha-tocopherol on acute pancreatitis in rat

Özgül H, Tatar C1, Özer B, Aydın H, Sarı S, Özer SP

Ulus Travma Acil Cerrahi Derg. 2019 Jan;25(1):1-6. doi: 10.5505/tjtes.2018.30413.

Abstract

BACKGROUND:

Acute pancreatitis is a disease with high morbidity and mortality, despite all the advances in technology. The overall mortality rate of acute pancreatitis is 10%, whereas the mortality rate in infected necrotizing pancreatitis is approximately 35%. In this study, we aimed to establish acute pancreatitis in rats in order to try out the alpha-tocopherol treatment protocol and to reveal the results biochemically and histopathologically.

METHODS:

Twenty-four male male Sprague-Dawley rats weighing between 300 and 350 g were used in the study. In Group 1, 80 µg/kg of normal saline was subcutaneously injected into eight rats; in Group 2, 80 µg/kg of cerulein was subcutaneously injected into eight rats; and in Group 3, 80 µg/kg of cerulein was subcutaneously injected into eight rats. In addition, 30 mg/kg of alpha-tocopherol was intraperitoneally injected into eight rats.

RESULTS:

The mean Schoenberg score, serum amylase, and lipase and Neutrophil Gelatinase-Associated Lipocalin (NGAL) levels were statistically significantly higher in Group 2 than in Group 1. The mean Schoenberg score and serum amylase and lipase levels were statistically significantly lower in Group 3 than in Group 2.

CONCLUSION:

In this experimental study rat model of cerulein-induced acute pancreatitis, 30 mg/kg of alpha-tocopherol was injected intraperitoneally to examine its effect on pancreatitis. The improvement was observed in the histopathological examination of pancreatic tissues. We think that alpha-tocopherol may have a therapeutic effect on pancreatic tissue.

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Tocopherol Emulsions as Functional Autoantigen Delivery Vehicles Evoke Therapeutic Efficacy in Experimental Autoimmune Encephalomyelitis.

Griffin JD, Christopher MA, Thati S, Salash JR, Pressnall MM, Weerasekara DB, Lunte SM, Berkland CJ

Mol Pharm. 2019 Jan 7. doi: 10.1021/acs.molpharmaceut.8b00887. [Epub ahead of print]

Abstract

Contemporary approaches to treating autoimmune diseases like Multiple Sclerosis broadly modulate the immune system and leave patients susceptible to severe adverse effects. Antigen-specific immunotherapies (ASIT) offer a unique opportunity to selectively suppress autoreactive cell populations, but have suffered from marginal efficacy even when employing traditional adjuvants to improve delivery. The development of immunologically active antigen delivery vehicles could potentially increase the clinical success of antigen-specific immunotherapies. An emulsion of the antioxidant tocopherol delivering an epitope of proteolipid protein autoantigen (PLP139-151) yielded significant efficacy in mice with experimental autoimmune encephalomyelitis (EAE). In vitro studies indicated tocopherol emulsions reduced oxidative stress in antigen presenting cells. Ex vivo analysis revealed that tocopherol emulsions shifted cytokines responses in EAE splenocytes. In addition, IgG responses against PLP139-151 were increased in mice treated with tocopherol emulsions delivering the antigen suggesting a possible skew in immunity. Overall, tocopherol emulsions provide a functional delivery vehicle for ASIT capable of ameliorating autoimmunity in a murine model.

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An open letter to Jeremy Hunt on palm oil

It is understandable if the Western edible oil industry launches a vicious campaign against palm oil out of commercial interest, even if lies and half-truths are employed. But when governments side with the for-profit industry in phasing out the import of palm oil without careful consideration of the facts, it calls into question the fairness and democratic principles that Western countries often preach.

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Tocopherols and Tocotrienols (Vitamin E) – The Lipid Web

Tocopherols and tocotrienols constitute a series of related benzopyranols (or methyl tocols) that are synthesised in plants and other photosynthetic organisms, where they have many important functions. First described in 1922 as a dietary factor essential to prevent fetal reabsorption in rats, it was soon understood that they contained a vitamin (vitamin E) that is essential for innumerable aspects of animal development. Tocopherols are now known to be powerful lipid-soluble antioxidants, but only one isomer, i.e. α-tocopherol, is recognized as having vitamin E activity. In addition, this has regulatory roles in signal transduction and gene expression in animal tissues. Vegetable oils are a major dietary source.

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Kinetic Study of the Quenching Reaction of Singlet Oxygen by Eight Vegetable Oils in Solution

Mukai K, Ohara A, Ito J, Hirata M, Kobayashi E, Nakagawa K, Nagaoka SI

J Oleo Sci. 2019 Jan 1;68(1):21-31. doi: 10.5650/jos.ess18179. Epub 2018 Dec 12.

Abstract

A kinetic study of the reaction of singlet oxygen (1O2) with eight vegetable oils 1-8 containing different concentrations of tocopherols (Tocs) and tocotrienols (Toc-3s) was performed. The second-order rate constants (kQ) for the reaction of 1O2 with vegetable oils 1-8 (rice bran, perilla, rape seed, safflower, grape seed, sesame, extra virgin olive, and olive oils) were measured in ethanol/chloroform/D2O (50:50:1, v/v/v) solution at 35°C using UV-vis spectrophotometry. Furthermore, comparisons of kQ values determined for the above oils 1-8 with the sum of the product {∑kQAO-i [AO-i]/105} of the kQAO-i values obtained for each antioxidant (AO-i) and concentration (in mg/100 g) ([AO-i]/105) of AO-i (Tocs and Toc-3s) contained in the oils 1-8 were performed. The observed kQ values were not reproduced by the kQ values calculated using only the concentrations of the four Tocs and Toc-3s. These results suggest that the contribution of fatty acids contained in the oils 1-8 is also necessary to fully explain the kQ values. Recently, the second-order rate constants (kS) for the reaction of aroxyl radical (ArO・) with the same vegetable oils 1-8 were measured in the same solvent at 25℃ using stopped-flow spectrophotometry (Ref. 23). The kS values obtained could be well explained as the sum of the product {Σ kSAO-i [AO-i]/105} of the kSAO-i and the [AO-i]/105 of AO-i (Tocs and Toc-3s) contained in the vegetable oils.

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Foods High in Alpha-Tocopherol

Alpha-tocopherol is an alternative name for vitamin E, which has many important functions in your body. A potent antioxidant, alpha-tocopherol protects you from potentially damaging free radicals, while also boosting your immune system to help you fight off viruses and pathogenic bacteria. It also helps your body make new red blood cells and widens your blood vessels, potentially lowering your risk of developing blood clots. The best way to obtain vitamin E, according to the National Institutes of Health, is to consume vitamin E-rich foods.

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The antioxidant effects of Hydroxytyrosol and Vitamin E on pediatric NAFLD, in a clinical trial: a new treatment?

Nobili V, Alisi A, Mosca A, Crudele A, Zaffina S, Denaro M, Smeriglio A, Trombetta D

Antioxid Redox Signal. 2018 Dec 27. doi: 10.1089/ars.2018.7704. [Epub ahead of print]

Abstract

TRIAL DESIGN:

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. Several studies suggest that the improvement of oxidative stress is suggested as a possible therapeutic strategy for paediatric NASH. We performed a randomized double-blind placebo-controlled trial to test the potential efficacy, assessed by improvement of oxidative-stress parameters and liver ultrasound, and tolerability of a mixture of vitamin E and Hydroxytyrosol (HXT) in adolescents with biopsy-proven NAFLD.

METHODS:

440 consecutive patients were screened, 80 of these with biopsy-proven NAFLD were enrolled. Forty patients received an oral dose of HXT and vitamin E and 40 children received the capsules of placebo, for 4 months.

RESULTS:

Seventy patients completed the study. Patients in the treatment arm showed a decrease of insulin-resistance, triglyceride levels, oxidative-stress parameters and steatosis grade. Noteworthy, the steatosis improvement correlates with the levels of advanced glycation end products and carbonylated proteins.

CONCLUSION:

The HXT and vitamin E treatment improved the main oxidative-stress parameters, insulin resistance and steatosis in children with NAFLD. The use of two natural molecules that may have antioxidant effects seems a promising strategy that could be easily diet integrated to improve NAFLD related liver damage in children.

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