Mitigation of radiation-induced lung injury by genistein and EUK-207.

Mitigation of radiation-induced lung injury by genistein and EUK-207.
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DOI:
10.3109/09553002.2011.583315
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发表时间:
2011-08
影响因子:
2.6
通讯作者:
Hill RP
Hill RP
中科院分区:
医学3区
文献类型:
--
作者:
Mahmood J;Jelveh S;Calveley V;Zaidi A;Doctrow SR;Hill RP

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我们检查了染料木黄酮和/或Eukarion(EUK)-207对辐射诱导的肺损伤的作用,并研究了辐射(PI)后0-14周(wks)的治疗是否会减轻晚期肺损伤。用10戈伊照射雌性SD大鼠的肺。EUK-207通过输注递送,染料木黄酮作为膳食补充剂在照射(PI)后立即开始递送并持续至PI 14周。在PI 0、4、8、14和28周处死大鼠。在28周时监测呼吸频率,通过肺羟脯氨酸含量评估肺纤维化,通过微核(MN)试验和8-羟基-2-脱氧鸟苷(8-OHdG)水平评估DNA损伤。免疫组化法检测细胞因子白细胞介素(IL)-1α、IL-1β、IL-6、肿瘤坏死因子(TNF)-α和转化生长因子(TGF)-β1的表达及巨噬细胞活化情况。在肺部炎症阶段和后期纤维化阶段,两种药物治疗均显著降低了在辐照大鼠中观察到的呼吸频率增加。药物处理从4-14周减少微核(MN)形成,但到28周,MN水平再次增加。在所有时间点,药物治疗动物的8-OHdG水平均较低。在所有药物处理的大鼠中,羟脯氨酸含量和活化的巨噬细胞水平在28周时降低。治疗对细胞因子表达的影响有限。染料木黄酮和EUK-207可以提供放射诱导的肺损伤的部分缓解,直到至少28周PI,甚至在14周PI停止治疗后。
We examined the effects of genistein and/or Eukarion (EUK)-207 on radiation-induced lung damage and investigated whether treatment for 0–14 weeks (wks) post-irradiation (PI) would mitigate late lung injury. The lungs of female Sprague-Dawley (SD) rats were irradiated with 10 Gy. EUK-207 was delivered by infusion and genistein was delivered as a dietary supplement starting immediately after irradiation (PI) and continuing until 14 wks PI. Rats were sacrificed at 0, 4, 8, 14 and 28 wks PI. Breathing rate was monitored and lung fibrosis assessed by lung hydroxyproline content at 28 wks. DNA damage was assessed by micronucleus (MN) assay and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. The expression of the cytokines Interleukin (IL)-1α, IL-1β, IL-6, Tumor necrotic factor (TNF)-α and Transforming growth factor (TGF)-β1, and macrophage activation were analysed by immunohistochemistry. Increases in breathing rate observed in the irradiated rats were significantly reduced by both drug treatments during the pneumonitis phase and the later fibrosis phase. The drug treatments decreased micronuclei (MN) formation from 4–14 wks but by 28 wks the MN levels had increased again. The 8-OHdG levels were lower in the drug treated animals at all time points. Hydroxyproline content and levels of activated macrophages were decreased at 28 wks in all drug treated rats. The treatments had limited effects on the expression of the cytokines. Genistein, and EUK-207 can provide partial mitigation of radiation-induced lung damage out to at least 28 wks PI even after cessation of treatment at 14 wks PI.
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