Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD(R) in mice.

Sanchita P. Ghosh, Shilpa Kulkarni, Michael W. Perkins, Kevin Hieber, Roli L. Pessu, Kristen Gambles, Manoj Maniar, Tzu Cheg Kao, Thomas M. Seed, K. Sree Kumar

Research output: Contribution to journalArticle

34 Scopus citations

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 vehicle-treated 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.

Original languageEnglish (US)
Pages (from-to)526-536
Number of pages11
JournalJournal of radiation research
Volume53
Issue number4
DOIs
StatePublished - Jul 2012

ASJC Scopus subject areas

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis

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    Ghosh, S. P., Kulkarni, S., Perkins, M. W., Hieber, K., Pessu, R. L., Gambles, K., Maniar, M., Kao, T. C., Seed, T. M., & Kumar, K. S. (2012). Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD(R) in mice. Journal of radiation research, 53(4), 526-536. https://doi.org/10.1093/jrr/rrs001