Monthly Archives: July 2013

γ-Tocotrienol Attenuates Triglyceride through Effect on Lipogenic Gene Expressions in Mouse Hepatocellular Carcinoma Hepa 1-6

Burdeos, GC, Nakagawa K, Watanabe A, Kimura F, Miyazawa T.

J Nutr Sci Vitaminol, 2013; 59(2):148-151,

Summary

Vitamin E is the generic name for tocopherol (Toc) and tocotrienol (T3), which have saturated and unsaturated side chains, respectively. Such differences allow T3 to be different from Toc in terms of their functions. T3 has been known to attenuate cholesterol (Cho) level by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR). Recent reports also showed the efficacy of T3 in improving triglyceride (TG) profiles in both in vivo and in vitro studies. However the mechanism involved in this biological activity is still unclear and needs to be further investigated. In the present study, we elucidated the effect of γ-T3 on lipid levels and lipogenic gene expressions in mouse hepatocellular carcinoma Hepa 1-6. γ-T3 showed attenuation of TG through effect on fatty acid synthas, sterol regulatory element-binding transcription factor 1, stearoyl CoA desaturase 1, and carnitine palmitoyl. In contrast, the Cho level remained unchanged. These results expanded our previous finding of lipid-lowering effects of T3, especially for TG. Therefore, T3 is a potential lipid-lowering compound candidate with realistic prospects for its use as a therapy for lipid-related diseases in humans.

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α-Tocopherol does not Accelerate Depletion of γ-Tocopherol and Tocotrienol or Excretion of their Metabolites in Rats

Uchida T, Nomura S, Sakuma E, Hanzawa F, Ikeda S.

Lipids (2013) 48:687–695

Summary: From an enzyme kinetic study using rat liver microsomes, α-tocopherol has been suggested to accelerate the other vitamin E catabolism by stimulating vitamin E ω-hydroxylation, the late limiting reaction of the vitamin E catabolic pathway. To test the effect of α-tocopherol on catabolism of the other vitamin E isoforms in vivo, we determined whether α-tocopherol accelerates depletion of γ-tocopherol and tocotrienol and excretion of their metabolites in rats. Male Wistar rats were fed a γ-tocopherol-rich diet for 6 weeks followed by a γ-tocopherol-free diet with or without α-tocopherol for

7 days. Intake of γ-tocopherol-free diets lowered γ-tocopherol concentrations in serum, liver, adrenal gland, small intestine, and heart, but there was no effect of dietary α-tocopherol on γ-tocopherol concentrations. The level of urinary excretion of γ-tocopherol metabolite was not affected by dietary α-tocopherol. Next, the effect of α-tocopherol on tocotrienol depletion was examined using rats fed a tocotrienol-rich diet for 6 weeks. Subsequent intake of a tocotrienol-free diet with or without α-tocopherol for 7 days depleted concentrations of α- and γ-tocotrienol in serum and tissues, which was accompanied by a decrease in the excretion of γ-tocotrienol metabolite.

However, neither the tocotrienol concentration nor c-tocotrienol metabolite excretion was affected by dietary α-tocopherol. These data showed that dietary α-tocopherol did not accelerate the depletion of γ-tocopherol and tocotrienol and their metabolite excretions, suggesting that the positive effect of α-tocopherol on vitamin E ω-hydroxylase is not sufficient to affect the other isoform concentrations in tissues.

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Vitamin E: tocopherols and tocotrienols as potential radiation countermeasures.

Singh VK, Beattie LA, Seed TM.

J Radiat Res, 2013 May 8. [Epub ahead of print]

Summary

Despite the potential devastating health consequences of intense total-body irradiation, and the decades of research, there still remains a dearth of safe and effective radiation countermeasures for emergency, radiological/nuclear contingencies that have been fully approved and sanctioned for use by the US FDA. Vitamin E is a well-known antioxidant, effective in scavenging free radicals generated by radiation exposure. Vitamin E analogs, collectively known as tocols, have been subject to active investigation for a long time as radioprotectors in patients undergoing radiotherapy and in the context of possible radiation accidents or terrorism scenarios. Eight major isoforms comprise the tocol group: four tocopherols and four tocotrienols. A number of these agents and their derivatives are being investigated actively as radiation countermeasures using animal models, and several appear promising. Although the tocols are well recognized as potent antioxidants and are generally thought to mediate radioprotection through ‘free radical quenching’, recent studies have suggested several alternative mechanisms: most notably, an ‘indirect effect’ of tocols in eliciting specific species of radioprotective growth factors/cytokines such as granulocyte colony-stimulating factor (G-CSF). The radioprotective efficacy of at least two tocols has been abrogated using a neutralizing antibody of G-CSF. Based on encouraging results of radioprotective efficacy, laboratory testing of γ-tocotrienolhas moved from a small rodent model to a large nonhuman primate model for preclinical evaluation. In this brief review we identify and discuss selected tocols and their derivatives currently under development as radiation countermeasures, and attempt to describe in some detail their in vivo efficacy.

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