Radioprotective efficacy of tocopherol succinate is mediated through granulocyte-colony stimulating factor

Identification of Granulocyte Colony-Stimulating Factor and Interleukin-6 as Candidate Biomarkers of CBLB502 Efficacy as a Medical Radiation Countermeasure

“…G-CSF is available as a treatment agent in current radiation countermeasure stockpiles that have been developed in the United States and by the World Health Organization (Dainiak, 2010). Recently, we found that G-CSF is a principal mediator of the radioprotective activity of tocopherol succinate (Singh et al, 2010(Singh et al, , 2011, 5-androstenediol, and ␥-tocotrienol (Singh et al, 2012;V. K. Singh and M. H. Whitnall, unpublished observations).…”

“…C57BL/6J mice (n ϭ 40 per group) were irradiated with 9.5 Gy of TBI, and 22 h afterward, treated with either rat anti-mouse G-CSF monoclonal antibodies (IgG1), rat anti-mouse anti-IL-6 antibodies (IgG1), or a control rat anti-mouse nonspecific IgG1. All antibodies were administered intraperitoneally by using a previously established effective dose (Neta et al, 1992;Singh et al, 2010Singh et al, , 2011 of 500 g/mouse. Two hours later (24 h after TBI), all mice in these groups were injected intravenously with 60 g/kg CBLB502.…”

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

“…Mice were placed in ventilated Plexiglas boxes compartmentalized to accommodate eight mice per box and exposed to bilateral irradiation in the AFRRI cobalt-60 facility at a dose rate of 0.6 Gy/min (Singh et al, 2011). Animals were exposed to a dose of 9.2 Gy (LD 90/30 dose for CD2F1 mice).…”

“…The third group did not receive a second injection (G-CSF antibody or isotype), and a fourth group received only vehicle. Blood was harvested from mice 24 h after DT3 injection (or 16 h after G-CSF neutralizing antibody or isotype administration) based on previously published work (Singh et al, 2011;Kulkarni et al, 2013). To analyze whether the G-CSF antibody specifically neutralized circulating G-CSF in peripheral blood, serum samples were analyzed for IL-1β, IL-6, IL-10, IL-12(p70), G-CSF, GM-CSF, KC, and TNF-α by multiplex Luminex.…”

A semiquinone glucoside derivative isolated fromBacillussp. INM-1 provides protection against 5-fluorouracil-induced immunotoxicity

“…G-CSF is known to activate several signaling pathways including pro-survival, proliferation, differentiation, and mobilization of stem and progenitor cells from the bone marrow to the spleen and then subsequently to the bloodstream (Singh et al, 2011). Here, a significant diminution in G-CSF presence was observed in the serum, spleen, and bone marrow cells of the mice administered with 5-FU (Figures 1, 4, and 7).…”