Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD(R) in mice.
Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD(R) in mice.
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DOI：
10.1093/jrr/rrs001
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发表时间：
2012-07
影响因子：
2
通讯作者：
Kumar KS
中科院分区：
文献类型：
--
作者：
Ghosh SP;Kulkarni S;Perkins MW;Hieber K;Pessu RL;Gambles K;Maniar M;Kao TC;Seed TM;Kumar KS
本研究的目的是评估全身辐射后Ex-RAD®（也称为ON01210.Na（4-羧基苯乙烯基-4-氯苄基砜，钠盐））对造血和胃肠道损伤的恢复。在我们以前的研究中，我们报道了Ex-RAD，一种小分子辐射防护剂，提高了暴露于γ辐射的小鼠的存活率，并通过抑制培养细胞中辐射诱导的蛋白53（p53）表达来预防辐射诱导的细胞凋亡。我们扩大了这项研究，以确定最佳有效剂量，剂量减少因子（DRF），血液和胃肠道保护，并在体内抑制p53信号。在辐射前24小时15分钟给予总计500 mg/kg的Ex-RAD，导致DRF为1.16。通过外周血细胞的加速恢复和骨髓中粒细胞-巨噬细胞集落形成单位（GM-CFU）的保护监测，Ex-RAD改善了辐射诱导的造血损伤。免疫印迹分析表明，Ex-RAD处理抑制p53磷酸化。与溶剂处理的小鼠相比，Ex-RAD处理减少了放射损伤后空肠中末端脱氧核苷酸转移酶介导的dUTP缺口末端标记试验（TUNEL）阳性细胞。最后，在13和14戈伊下，与载体对照相比，Ex-RAD保存了肠隐窝细胞。结果表明，Ex-RAD可改善辐射诱导的外周血细胞耗竭，促进骨髓恢复，降低脾脏p53信号，保护肠道免受辐射损伤。
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.
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DOI：
10.1016/s0360-3016(00)00744-6
发表时间：
2000-11-01
影响因子：
7
作者：
Hovdenak, N;Fajardo, LF;Hauer-Jensen, M
通讯作者：
Hauer-Jensen, M
影响因子：
3.1
作者：
BUELL, MG;HARDING, RK
通讯作者：
HARDING, RK
影响因子：
3.4
作者：
Kulkarni, Shilpa;Ghosh, Sanchita P.;Kumar, K. Sree
通讯作者：
Kumar, K. Sree
影响因子：
3.4
作者：
Berbée M;Fu Q;Boerma M;Wang J;Kumar KS;Hauer-Jensen M
通讯作者：
Hauer-Jensen M
影响因子：
13.5
作者：
BROWN, DQ;GRAHAM, WJ;SHAW, LM
通讯作者：
SHAW, LM