Alpha-tocopherol succinate protects mice from gamma-radiation by induction of granulocyte-colony stimulating factor

Abstract

The results indicate that G-CSF-induced by the administration of TS, mobilises hematopoietic stem cells and is responsible for the protection from ionising radiation.

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et al, 2010(Singh et al, , 2011, 5-androstenediol, and ␥-tocotrienol (Singh et al, 2012;V. K. Singh and M. H. Whitnall, unpublished observations).…”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

“…The optimal drug dose for this study, 200 mg/kg for all three agents, was selected based on published reports (Satyamitra et al, 2011;Li et al, 2010;Ghosh et al, 2009;Singh et al, 2010). DT3 and GT3 formulations in 5% Tween-80 in saline were purchased from Yasoo Health, Inc. (Johnson City, TN, USA).…”

Progenitor Cells as a Bridging Therapy for Radiation Casualties

“…When both TS and AMD3100 were administered, they observed very high HSC mobilisation in peripheral blood. Their results demonstrate enhancement of lin -Sca-1 (Ly-6A/E), c-Kit (CD117) as well as double positive cells (Sca-1, c-Kit) in response to TS/AMD3100 administration 56 . HSC mobilisation by TS was comparable to that achieved by G-CSF.…”

“…TS also modulates the expression of various antioxidant genes and helps in hematopoietic recovery 54 . The authors demonstrated that TS stimulates G-CSF production and showed that TS-mediated protection can be neutralised by administration of G-CSF antibody 53,55,56 . The authors hypothesised that TS mobilises progenitor cells into the peripheral circulation.…”