Alpha-tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice

Abstract

The purpose of this study was to elucidate the role of alpha-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5–12.5 Gy) of 60Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans.

New Approaches to Radiation Protection

“…We also observed that the infusion of PBMC from TS- and AMD3100-injected mice significantly inhibited apoptosis, increased cell proliferation in the analyzed tissues of recipient mice, and inhibited bacterial translocation to various organs compared to mice receiving cells from vehicle-mobilized cells ( 189 ). Most recently, we have observed that TS-mobilized progenitors mitigate radiation combined injury (radiation and wound) ( 190 ). In aggregate, these rodent-based studies strongly suggest that TS has the capacity to mobilize progenitors from marrow into the blood.…”

Protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury

“…We think OA may cooperate with PLA or ALA to reduce the radiation-induced intestinal injury and increase the survival time. α-Vitamin E has been suggested as a radioprotector for improving radiation-induced intestinal injury and wound healing [ 28 , 29 ]. Even though the seabuckthorn oil α-Vitamin E content is relatively lower than its fatty acids content, we speculate that α-Vitamin E might produce a synergistic effects on PLA- and ALA-mediated intestinal protection.…”

Personalized Radioproteomics: Identification of a Protein Biomarker Signature for Preemptive Rescue by Tocopherol Succinate in CD34+ Irradiated Progenitor Cells Isolated from a Healthy Control Donor

“…Radiation dosimetry was based primarily on the alanine/EPR (electron paramagnetic resonance) system [ 21 , 22 ], currently accepted as one of the most accurate methods and used for intercomparison between national metrology institutions. The details of dosimetry have been described earlier [ 23 ]. CD34 + cells were exposed to either 0 or 2 Gy (0.6 Gy/min) 60 Co γ-radiation.…”