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

Int J Radiat Biol. 2013 May;89(5):334-45. doi: 10.3109/09553002.2013.762137. Epub 2013 Feb 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Bacteria / drug effects
  • Bacteria / radiation effects
  • Cell Movement / drug effects*
  • Cell Movement / radiation effects
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • DNA Breaks / drug effects
  • DNA Breaks / radiation effects
  • Endotoxins / blood
  • Gamma Rays / adverse effects
  • Intestines / cytology
  • Intestines / drug effects*
  • Intestines / microbiology
  • Intestines / radiation effects*
  • Jejunum / cytology
  • Jejunum / drug effects
  • Jejunum / radiation effects
  • Male
  • Mice
  • Radiation Injuries / prevention & control
  • Radiation-Protective Agents / pharmacology*
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / radiation effects
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / radiation effects
  • Whole-Body Irradiation / adverse effects*
  • alpha-Tocopherol / pharmacology*

Substances

  • Endotoxins
  • Radiation-Protective Agents
  • alpha-Tocopherol