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

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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
StatePublished - Jul 2012
Externally publishedYes

Fingerprint

mice
Radiation
damage
radiation
radiation injuries
proteins
blood cells
Radiation Injuries
spleen
bone marrow
recovery
dosage
Blood Cells
vehicles
Proteins
Spleen
Bone Marrow
intestines
Granulocyte-Macrophage Progenitor Cells
phosphorylation

ASJC Scopus subject areas

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

Cite this

Ghosh, S. P., Kulkarni, S., Perkins, M. W., Hieber, K., Pessu, R. L., Gambles, K., ... 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.

Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD(R) in mice. / Ghosh, Sanchita P.; Kulkarni, Shilpa; Perkins, Michael W.; Hieber, Kevin; Pessu, Roli L.; Gambles, Kristen; Maniar, Manoj; Kao, Tzu Cheg; Seed, Thomas M.; Kumar, K. Sree.

In: Journal of Radiation Research, Vol. 53, No. 4, 07.2012, p. 526-536.

Research output: Contribution to journalArticle

Ghosh, SP, Kulkarni, S, Perkins, MW, Hieber, K, Pessu, RL, Gambles, K, Maniar, M, Kao, TC, Seed, TM & Kumar, KS 2012, 'Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD(R) in mice.', Journal of Radiation Research, vol. 53, no. 4, pp. 526-536.
Ghosh, Sanchita P. ; Kulkarni, Shilpa ; Perkins, Michael W. ; Hieber, Kevin ; Pessu, Roli L. ; Gambles, Kristen ; Maniar, Manoj ; Kao, Tzu Cheg ; Seed, Thomas M. ; Kumar, K. Sree. / Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD(R) in mice. In: Journal of Radiation Research. 2012 ; Vol. 53, No. 4. pp. 526-536.
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