title: Radioprotective efficacy of tocopherol succinate is mediated through granulocyte-colony stimulating factor.
abstract: The purpose of this study was to elucidate the role of granulocyte colony-stimulating factor (G-CSF) induced by α-tocopherol succinate (TS) in protecting mice from total-body irradiation. CD2F1 mice were injected with a radioprotective dose of TS and the levels of cytokine in serum induced by TS were determined by multiplex Luminex. Neutralization of G-CSF was accomplished by administration of a G-CSF antibody and confirmed by cytokine analysis. The role of G-CSF on gastrointestinal tissue protection afforded by TS after irradiation (11 Gy, 0.6 Gy/min of 60Co γ-radiation) was determined by analysis of jejunum histopathology for crypt, villi, mitotic figures, apoptosis, and cell proliferation. Our results demonstrate that TS protected mice against high doses of radiation-induced gastrointestinal damage and TS also induced very high levels of G-CSF and keratinocyte-derived chemokine (KC) production in peripheral blood 24 h after subcutaneous administration. When TS-injected mice were administered a neutralizing antibody to G-CSF, there was complete neutralization of G-CSF in circulating blood, and the protective effect of TS was significantly abrogated by G-CSF antibody. Histopathology of jejunum from TS-injected and irradiated mice demonstrated protection of gastrointestinal tissue, yet the protection was abrogated by administration of a G-CSF antibody. In conclusion, our current study suggests that induction of G-CSF resulting from TS administration is responsible for protection from 60Co γ-radiation injury.
authors: Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA.
authors: Pankaj K
authors: PK
authors: Singh
authors: Stephen Y
authors: SY
authors: Wise
authors: Elizabeth J
authors: EJ
authors: Ducey
authors: Darren S
authors: DS
authors: Brown
authors: Vijay K
authors: VK
authors: Singh
mesh_terms: D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D024505:Tocopherols / Q000494:pharmacology*
chemical_list: D011837:Radiation-Protective Agents; D016179:Granulocyte Colony-Stimulating Factor; D024505:Tocopherols