Radioprotective properties of tocopherol succinate against ionizing radiation in mice

Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, 8901 Wisconsin Ave, Bethesda, MD 20889-5603, USA.
Journal of Radiation Research (Impact Factor: 1.8). 10/2012; 54(2). DOI: 10.1093/jrr/rrs088
Source: PubMed


Threats of nuclear and other radiologic exposures have been increasing but no countermeasure for acute radiation syndrome has been approved by regulatory authorities. In prior publications we have demonstrated the efficacy of tocopherol succinate (TS) as a promising radiation countermeasure with the potential to protect against lethal doses of ionizing radiation exposure. The aim of this study was to gain further insight regarding how TS protects mice against a lethal dose of radiation. CD2F1 mice were injected subcutaneously with 400 mg/kg of TS, and 24 h later exposed to (60)Co γ-radiation. Intestinal tissues or spleen/thymus were harvested after irradiation and analyzed for CD68-positive inflammatory cells and apoptotic cells by immunostaining of jejunal cross-sections. Comet assay was used to analyze DNA damage in various tissues. Phospho-histone H3 (pH3) and the proliferating cell nuclear antigen (PCNA) were used as mitotic markers for immunostaining jejunal cross-sections. We observed that injecting TS significantly decreased the number of CD68-positive cells, DNA damage and apoptotic cells (BAX, caspase 3 and cleaved poly(ADP-ribose) polymerase-positive cells) as judged by various apoptotic pathway markers. TS treatment also increased proliferating cells in irradiated mice. Results of this study further support our contention that TS protects mice against lethal doses of ionizing radiation by inhibiting radiation-induced apoptosis and DNA damage while enhancing cell proliferation.

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Available from: Pankaj Singh, Mar 12, 2014
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    • "It is possible that GTDMG induces radioprotective cytokines such as G-CSF and growth factors in the way that alpha-tocopherol succinate does [41], although as yet we do not have experimental data to support this. Several other mechanisms have been considered to explain the effect of tocopherols, tocotrienols and their derivatives in their action as radiation countermeasures [33, 35–37, 42, 43]. One such mechanism is based on the antioxidant property. "
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