title: Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD(R) 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 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.
authors: Armed Forces Radiobiology Research Institute, USUHS, Bethesda, MD 20889-5603, USA. ghosh@afrri.usuhs.mil
authors: Sanchita P
authors: SP
authors: Ghosh
authors: Shilpa
authors: S
authors: Kulkarni
authors: Michael W
authors: MW
authors: Perkins
authors: Kevin
authors: K
authors: Hieber
authors: Roli L
authors: RL
authors: Pessu
authors: Kristen
authors: K
authors: Gambles
authors: Manoj
authors: M
authors: Maniar
authors: Tzu-Cheg
authors: TC
authors: Kao
authors: Thomas M
authors: TM
authors: Seed
authors: K Sree
authors: KS
authors: Kumar
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D041981:Gastrointestinal Tract / Q000528:radiation effects*; D055014:Granulocyte-Macrophage Progenitor Cells / Q000378:metabolism; D006413:Hematopoietic System / Q000528:radiation effects*; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009503:Neutropenia / Q000188:drug therapy*; D010766:Phosphorylation; D011832:Radiation Injuries / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013154:Spleen / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
chemical_list: C520364:(E)-4-carboxystyryl-4-chlorobenzylsulfone, sodium salt; D011837:Radiation-Protective Agents; D013449:Sulfonamides