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

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. Multiplex Luminex wa...

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Bibliographic Details
Published in:Life sciences (1973) 2014-03, Vol.98 (2), p.113-122
Main Authors: Singh, Vijay K., Wise, Stephen Y., Scott, Jessica R., Romaine, Patricia L.P., Newman, Victoria L., Fatanmi, Oluseyi O.
Format: Article
Language:English
Subjects:
Animals
Cytokines - metabolism
Delta-tocotrienol
Gamma-radiation
Gene Expression Regulation - drug effects
Granulocyte colony-stimulating factor
Granulocyte Colony-Stimulating Factor - metabolism
Infusions, Subcutaneous
Male
Mice
Radiation
Radiation, Ionizing
Radiation-Protective Agents - pharmacology
Tocols
Vitamin E - analogs & derivatives
Vitamin E - chemistry
Vitamin E - pharmacology
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Summary: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. Multiplex Luminex was used to analyze cytokines induced by DT3 and other tocols (gamma-tocotrienol 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. 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. Our study findings suggest that G-CSF induced by DT3 mediates its radioprotective efficacy against ionizing radiation in mice.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2014.01.065