Cebpd Is Essential for Gamma-Tocotrienol Mediated Protection Against Radiation-Induced Hematopoietic and Intestinal Injury

Gamma-tocotrienol (GT3) confers protection against ionizing radiation (IR)-induced injury. However, the molecular targets that underlie the protective functions of GT3 are not yet known. We have reported that mice lacking CCAAT enhancer binding protein delta () display increased mortality to IR due to injury to the hematopoietic and intestinal tissues and that protects from IR-induced oxidative stress and cell death. The purpose of this study was to investigate whether mediates the radio protective functions of GT3. We found that GT3-treated mice showed partial recovery of white blood cells compared to GT3-treated mice at 2 weeks post-IR. GT3-treated mice showed an increased loss of intestinal crypt colonies, which correlated with increased expression of inflammatory cytokines and chemokines, increased levels of oxidized glutathione (GSSG), S-nitrosoglutathione (GSNO) and 3-nitrotyrosine (3-NT) after exposure to IR compared to GT3-treated mice. is induced by IR as well as a combination of IR and GT3 in the intestine. Studies have shown that granulocyte-colony stimulating factor (G-CSF), mediates the radioprotective functions of GT3. Interestingly, we found that IR alone as well as the combination of IR and GT3 caused robust augmentation of plasma G-CSF in both and mice. These results identify a novel role for in GT3-mediated protection against IR-induced injury, in part via modulation of IR-induced inflammation and oxidative/nitrosative stress, which is independent of G-CSF.