Protection of radiation-induced damage to the hematopoietic system, small intestine and salivary glands in rats by JNJ7777120 compound, a histamine H4 ligand.
Protection of radiation-induced damage to the hematopoietic system, small intestine and salivary glands in rats by JNJ7777120 compound, a histamine H4 ligand.
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保护辐射引起的对造血系统的损害，大鼠小肠和唾液腺的损害，由组胺H4配体JNJ7777120大鼠造成。
DOI：
10.1371/journal.pone.0069106
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Medina VA
中科院分区：
文献类型：
--
作者：
Martinel Lamas DJ;Carabajal E;Prestifilippo JP;Rossi L;Elverdin JC;Merani S;Bergoc RM;Rivera ES;Medina VA
基于以前的数据组胺辐射防护作用的高辐射敏感性组织，在目前的工作中，我们的目的是调查的辐射防护潜力的H4 R配体，JNJ 7777120，电离辐射诱导的损伤和遗传毒性损伤的小肠，唾液腺和造血组织。为此，将大鼠分为4组。JNJ 7777120和JNJ 7777120辐照组从辐照前24小时开始每日皮下注射JNJ 7777120（10 mg/kg）。照射组采用~（137）Cs源单次全身照射5戈伊，照射后3天或30天处死动物。取出组织，固定，用苏木精和伊红染色或PAS染色，并评价组织学特征。免疫组化法检测细胞凋亡和凋亡标志物，微核试验检测DNA损伤。通过乙酰甲胆碱诱导的流涎来评价颌下腺（SMG）功能。结果表明，JNJ 7777120治疗减少了放射暴露后的粘膜萎缩和保留的绒毛和隐窝数量（240±8比165±10，P<0.01）。这种作用与肠隐窝中细胞凋亡和DNA损伤减少有关。JNJ 7777120可减少辐射诱导的再生障碍，保留骨髓成分，减少微核形成，并加速骨髓再生。此外，它还能降低外周血微核率（27±8比149±22，每1,000个红细胞，P<0.01）。JNJ 7777120完全逆转了辐射诱导的流涎减少，保留了具有正常组织学外观的腺体质量，并减少了SMG的细胞凋亡和萎缩。JNJ 7777120对小肠、SMG和造血组织中辐射诱导的细胞毒性和遗传毒性损伤具有辐射保护作用，因此，对于接受放疗的患者可能具有临床价值。
Based on previous data on the histamine radioprotective effect on highly radiosensitive tissues, in the present work we aimed at investigating the radioprotective potential of the H4R ligand, JNJ7777120, on ionizing radiation-induced injury and genotoxic damage in small intestine, salivary glands and hematopoietic tissue. For that purpose, rats were divided into 4 groups. JNJ7777120 and JNJ7777120-irradiated groups received a daily subcutaneous JNJ7777120 injection (10 mg/kg) starting 24 h before irradiation. Irradiated groups received a single dose of 5 Gy on whole-body using Cesium-137 source and were sacrificed 3 or 30 days after irradiation. Tissues were removed, fixed, stained with hematoxylin and eosin or PAS staining and histological characteristics were evaluated. Proliferative and apoptotic markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate DNA damage. Submandibular gland (SMG) function was evaluated by methacholine-induced salivation. Results indicate that JNJ7777120 treatment diminished mucosal atrophy and preserved villi and the number of crypts after radiation exposure (240±8 vs. 165±10, P<0.01). This effect was associated to a reduced apoptosis and DNA damage in intestinal crypts. JNJ7777120 reduced radiation-induced aplasia, preserving medullar components and reducing formation of micronucleus and also it accelerated bone marrow repopulation. Furthermore, it reduced micronucleus frequency in peripheral blood (27±8 vs. 149±22, in 1,000 erythrocytes, P<0.01). JNJ7777120 completely reversed radiation-induced reduced salivation, conserving glandular mass with normal histological appearance and reducing apoptosis and atrophy of SMG. JNJ7777120 exhibits radioprotective effects against radiation-induced cytotoxic and genotoxic damages in small intestine, SMG and hematopoietic tissues and, thus, could be of clinical value for patients undergoing radiotherapy.
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影响因子：
2.6
作者：
Medina, Vanina A.;Croci, Maximo;Rivera, Elena S.
通讯作者：
Rivera, Elena S.
DOI：
10.1152/ajpgi.00480.2003
发表时间：
2004-07-01
影响因子：
4.5
作者：
Gresz, V;Kwon, TH;Nielsen, S
通讯作者：
Nielsen, S
影响因子：
--
作者：
Stegaev, V.;Sillat, T.;Konttinen, Y. T.
通讯作者：
Konttinen, Y. T.
影响因子：
1.3
作者：
De la Cal, C.;Fernandez-Solari, J.;Elverdin, J. C.
通讯作者：
Elverdin, J. C.
影响因子：
3.4
作者：
Fliedner, TM;Graessle, D;Reimers, K
通讯作者：
Reimers, K