Comparative antioxidant activity of tocotrienols and the novel chromanyl-polyisoprenyl molecule FeAox-6 in isolated membranes and intact cells

Palozza, Paola; Verdecchia, Sara; Avanzi, Luca; Vertuani, Silvia; Serini, Simona; Iannone, Anna; Manfredini, Stefano

doi:10.1007/s11010-005-9020-7

Cited by 63 publications

(52 citation statements)

References 43 publications

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“…The present study, using a chronic experimental setup where animals were fed TRF and tocotrienols for a period of 4 wk, confirmed this previous observation and further demonstrated that tocotrienol isomers present in TRF differentially stabilize proteasomes with the ␦-isomer being the most protective and ␣-and ␥-isomers providing protection midway between baseline and postischemic hearts, which surprisingly is reverse to their respective cardioprotective efficacies. It is not clear whether this is related to the differential regulation of proteasome subunits, but it could be related to differential compartmentalization (30) or antioxidant potential, with the ␦-isomer reported to be the most effective (19).…”

Section: Discussionmentioning

confidence: 99%

Cardioprotection with palm oil tocotrienols: comparision of different isomers

Das¹,

Lekli²,

M³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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A recent study from our laboratory indicated the cardioprotective ability of the tocotrienolrich fraction (TRF) from red palm oil. The present study compared cardioprotective abilities of different isomers of tocotrienol against TRF as recently tocotrienol has been found to function as a potent neuroprotective agent against stroke. Rats were randomly assigned to one of the following groups: animals were given, by gavage, either 0.35%, 1%, or 3.5% TRF for two different periods of time (2 or 4 wk) or 0.03, 0.3, and 3 mg/kg body wt of one of the isomers of tocotrienol (␣, ␥, or ␦) for 4 wk; control animals were given, by gavage, vehicle only. After 2 or 4 wk, rats were killed, and their hearts were then subjected to 30 min of global ischemia followed by 2 h of reperfusion. Dose-response and time-response experiments revealed that the optimal concentration for TRF was 3.5% TRF and 0.3 mg/kg body wt of tocotrienol given for 4 wk. TRF as well as all the isomers of tocotrienol used in our study provided cardioprotection, as evidenced by their ability to improve postischemic ventricular function and reduce myocardial infarct size. The ␥-isoform of tocotrienol was the most cardioprotective of all the isomers followed by the ␣-and ␦-isoforms. The molecular mechanisms of cardioprotection afforded by tocotrienol isoforms were probed by evaluating their respective abilities to stabilize the proteasome, allowing it to maintain a balance between prodeath and prosurvival signals. Our results demonstrated that tocotrienol isoforms reduced c-Src but increased the phosphorylation of Akt, thus generating a survival signal.

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Section: Discussionmentioning

confidence: 99%

Cardioprotection with palm oil tocotrienols: comparision of different isomers

Das¹,

Lekli²,

M³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…The differential cell uptake of vitamin E forms could involve specific transporters such as the organic anion transport system (Negis et al 2007), but also direct membrane transfer and intramembrane diffusion and interaction mechanisms that appear to favor the uptake and bioactivity of HM T3 forms (Palozza et al 2006). The rapid and massive uptake of d-T3 and in general of HM forms in cancer cells may influence the lipid structure and key functional domains of the plasmalemma (Atkinson et al 2010).…”

Section: Metabolite Formation and Activitymentioning

confidence: 99%

Why tocotrienols work better: insights into the in vitro anti-cancer mechanism of vitamin E

et al. 2011

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The selective constraint of liver uptake and the sustained metabolism of tocotrienols (T3) demonstrate the need for a prompt detoxification of this class of lipophilic vitamers, and thus the potential for cytotoxic effects in hepatic and extra-hepatic tissues. Hypomethylated (c and d) forms of T3 show the highest in vitro and in vivo metabolism and are also the most potent natural xenobiotics of the entire vitamin E family of compounds. These stimulate a stress response with the induction of detoxification and antioxidant genes. Depending on the intensity of this response, these genes may confer cell protection or alternatively they stimulate a senescence-like phenotype with cell cycle inhibition or even mitochondrial toxicity and apoptosis. In cancer cells, the uptake rate and thus the cell content of these vitamers is again higher for the hypomethylated forms, and it is the critical factor that drives the dichotomy between protection and toxicity responses to different T3 forms and doses. These aspects suggest the potential for marked biological activity of hypomethylated ''highly metabolized'' T3 that may result in cytoprotection and cancer prevention or even chemotherapeutic effects. Cytotoxicity and metabolism of hypomethylated T3 have been extensively investigated in vitro using different cell model systems that will be discussed in this review paper as regard molecular mechanisms and possible relevance in cancer therapy.Keywords Tocotrienols Á Vitamin E Á Breast cancer Á Antioxidants Á Apoptosis Á Cell signaling Á Inflammation Á Metabolism Á Gene expression Á Cell redox T3 structure-function and specificity of actionIn the vitamin E family of molecules, tocotrienols (T3) are often considered of minor importance since these are less abundant than a and c tocopherol (TOH) in the circulation and in solid tissues. This has contributed to hinder our knowledge on the biological functions of this group of vitamers that is now regaining great interest, thanks to a number of recent studies that suggested health-promoting functions related with the cholesterol-lowering, cytoprotective, and anticarcinogenic effects of T3 [reviewed in (Aggarwal et al. (2010)].Structure-function studies demonstrate that many of these functions are more potent when the unsaturated (isoprenyl) side chain of T3 is combined with a hypomethylated (HM) chroman ring. The unsaturated chain characteristic of all the T3 forms confers well-defined physical and chemical characteristics that appear to include vitamer-specific interactions with other lipids and cell proteins (Atkinson

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“…It represents a family of compounds that is divided into two subgroups called tocopherols and tocotrienols, which act as important antioxidants that regulate peroxidation reactions and control free-radical production within the body (Palozza et al, 2006(Palozza et al, , 2008. This family of compounds has eight different isoforms that belong to two categories: four saturated analogues (α, β, γ, and δ) called tocopherols and four unsaturated analogues referred to as tocotrienols.…”

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confidence: 99%

Radioprotective efficacy of delta-tocotrienol, a vitamin E isoform, is mediated through granulocyte colony-stimulating factor

Singh

Wise²,

Scott³

et al. 2014

Life Sciences

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Newman, Victoria L.; and Fatanmi, Oluseyi O., "Radioprotective efficacy of delta-tocotrienol, a vitamin E isoform, is mediated through granulocyte colony-stimulating factor" (2014 Aims: The objectives of this study were to determine the cytokine induction by delta tocotrienol (DT3, a promising radiation countermeasure) and to investigate the role of granulocyte colony-stimulating factor (G-CSF) in its radioprotective efficacy against ionizing radiation in mice. Main methods:Multiplex Luminex was used to analyze cytokines induced by DT3 and other tocols (gammatocotrienol and tocopherol succinate) in CD2F1 mice. Mice were injected with an optimal dose of DT3 and a G-CSF antibody, and their 30-day survival against cobalt-60 gamma-irradiation was monitored. The neutralization of G-CSF by the administration of a G-CSF-specific antibody in DT3-injected mice was investigated by multiplex Luminex. Key findings: Our data demonstrate that DT3 induced high levels of various cytokines comparable to other tocols being developed as radiation countermeasures. DT3 significantly protected mice against ionizing radiation, and the administration of a G-CSF neutralizing antibody to DT3-treated animals resulted in the complete abrogation of DT3's radioprotective efficacy and neutralization of G-CSF in peripheral blood. Significance: Our study findings suggest that G-CSF induced by DT3 mediates its radioprotective efficacy against ionizing radiation in mice.Published by Elsevier Inc.

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Comparative antioxidant activity of tocotrienols and the novel chromanyl-polyisoprenyl molecule FeAox-6 in isolated membranes and intact cells

Cited by 63 publications

References 43 publications

Cardioprotection with palm oil tocotrienols: comparision of different isomers

Cardioprotection with palm oil tocotrienols: comparision of different isomers

Why tocotrienols work better: insights into the in vitro anti-cancer mechanism of vitamin E

Radioprotective efficacy of delta-tocotrienol, a vitamin E isoform, is mediated through granulocyte colony-stimulating factor

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