Serum proteomic signatures in non-human primates following 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 to
protect from radiation-induced injury is 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 to be promising in terms of its
antioxidant activity as well as its 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 of 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.