| Autor: |
Ghosh SP; Armed Forces Radiobiology Research Institute, USUHS, Bethesda, MD 20889-5603, USA. ghosh@afrri.usuhs.mil, Kulkarni S, Perkins MW, Hieber K, Pessu RL, Gambles K, Maniar M, Kao TC, Seed TM, Kumar KS |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of radiation research [J Radiat Res] 2012 Jul; Vol. 53 (4), pp. 526-36. Date of Electronic Publication: 2012 Jun 06. |
| DOI: |
10.1093/jrr/rrs001 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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