Serum Proteomic Signatures in Nonhuman Primates after Treatment with a Radiation Countermeasure and Exposure to a Partial- or Total-body Supralethal Radiation Dose

As countries face emerging conflicts and evaluate military strategies, the potential for nuclear-related accidents continues to rise, putting large populations of civilians at risk. As a result, the development of pharmaceuticals that can be administered prior to radiation exposure that protect from radiation-induced injury are of utmost importance. However, there are currently no prophylactic drugs that can be used to protect against radiation injury. One drug under advanced development, gamma-tocotrienol (GT3), has proved promising in terms of its antioxidant activity, accelerated hematopoietic recovery, and reduction of DNA damage in treated animals exposed to various doses of ionizing radiation. In this study, nonhuman primates (NHPs) were leveraged to investigate the protective effects of GT3 on proteomic profiles in conjunction with a supralethal dose (12 Gy) of either total-body irradiation (TBI) or partial-body irradiation (PBI), performed with 5% bone marrow sparing. Animals were treated with either GT3 or vehicle 24 h prior to irradiation, and blood samples were collected at various time points pre- and post-exposure to assess changes in serum proteomic profiles. Both PBI and TBI induced significant dysregulation to pathways related to extracellular matrix and organization, hemostasis, and immune response. Notably, administration of GT3 offered significant protection against radiation-induced damage by either partial- or total-body irradiation in these pathways. Overall, this study offers insight into the biochemical mechanisms of the drug, pathways and proteins adversely affected by radiation, and potential biomarkers that can be further investigated to accurately assess absorbed radiation doses in exposed populations.