Alpha-tocopherol succinate-mobilized progenitors improve intestinal integrity after whole body irradiation

Abstract

Purpose: The objective of this study was to elucidate the action of α-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating radiation-induced injuries.

Material and methods: CD2F1 mice were exposed to a high dose of radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMC) from TS- and AMD3100-injected mice after irradiation. Intestinal and splenic tissues were harvested after irradiation and cells of those tissues were analyzed for markers of apoptosis and mitosis. Bacterial translocation from gut to heart, spleen, and liver in TS-treated and irradiated mice was evaluated by bacterial culture.

Results: We 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. This study further supports our contention that the infusion of TS-mobilized progenitor-containing PBMC acts as a bridging therapy by inhibiting radiation-induced apoptosis, enhancing cell proliferation, and inhibiting bacterial translocation in irradiated mice.

Conclusions: We suggest that this novel bridging therapeutic approach that involves the infusion of TS-mobilized hematopoietic progenitors following acute radiation injury might be applicable to humans as well.

Keywords::

• Apoptosis
• bacterial translocation
• gamma-radiation
• irradiation
• progenitor cells
• mice
• mitosis
• transfusion

Acknowledgements

The opinions or assertions contained herein are the private views of the authors and are not necessarily those of the Armed Forces Radiobiology Research Institute (AFRRI), the Uniformed Services University of the Health Sciences, or the Department of Defense. We gratefully acknowledge Dr Cara Olsen for statistical help, and AFRRI's Veterinary Sciences Department and Cobalt Radiation Facility for their support. The authors are thankful to Dr Christopher R. Lissner, Dr John R. Gilstad, and Dr Mark H. Whitnall for helpful discussions and critical review of this manuscript. This study was supported by intramural awards RAB2CZ and RBB2GQ to VKS. PKS was supported by a fellowship from National Research Council, Washington, DC.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper