Amelioration of Radiation-Induced Hematopoietic and Gastrointestinal Damage by Ex-RAD (trademark) in Mice

Abstract

The aim of the present study was to assess recovery from hematopoietic and gastrointestinal damage by Ex-RAD , also known as ON01210.Na (4-carboxystyryl-4-chlorobenzylsulfone, sodium salt), after total body radiation. In our previous study, we reported that Ex-RAD, a small-molecule radioprotectant, enhances survival of mice exposed to gamma radiation, and prevents radiation-induced apoptosis as measured by the inhibition of radiation-induced protein 53 (p53) expression in cultured cells. We have expanded this study to determine best effective dose, dose-reduction factor (DRF), hematological and gastrointestinal protection, and in vivo inhibition of p53 signaling. A total of 500 mg/kg of Ex-RAD administered at 24 h and 15 min before radiation resulted in a DRF of 1.16. Ex-RAD ameliorated radiation-induced hematopoietic damage as monitored by the accelerated recovery of peripheral blood cells, and protection of granulocyte macrophage colony-forming units (GM-CFU) in bone marrow. Western blot analysis on spleen indicated that Ex- RAD treatment inhibited p53 phosphorylation. Ex-RAD treatment reduces terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay (TUNEL)-positive cells in jejunum compared with vehicletreated mice after radiation injury. Finally, Ex-RAD preserved intestinal crypt cells compared with the vehicle control at 13 and 14 Gy. The results demonstrated that Ex-RAD ameliorates radiation-induced peripheral blood cell depletion, promotes bone marrow recovery, reduces p53 signaling in spleen and protects intestine from radiation injury.

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Document Details

Document Type
Technical Report
Publication Date
Jun 06, 2012
Accession Number
ADA562661

Entities

People

  • K. S. Kumar
  • Kevin Hieber
  • Kristen Gambles
  • Manoj Maniar
  • Michael W. Perkins
  • Roli L. Pessu
  • Sanchita P. Ghosh
  • Shilpa Kulkarni
  • Thomas M. Seed
  • Tzu-cheg Kao

Organizations

  • Uniformed Services University of the Health Sciences

Tags

DTIC Thesaurus Topics

  • Blood
  • Blood Cells
  • Body Weight
  • Cell Count
  • Cells
  • Epithelial Cells
  • Gamma Rays
  • Granulocytes
  • Growth Factors
  • Hematopoietic System
  • Leukocytes
  • Peptides
  • Proteins
  • Radiation
  • Radiation Injuries
  • Stem Cells
  • Vitamin E

Fields of Study

  • Biology
  • Medicine
  • Physics

Readers

  • Nuclear and Radiation Engineering.
  • Polymer Science and Engineering.
  • Toxicology/Environmental Toxicology