Partial volume rat lung irradiation: The protective/mitigating effects of Eukarion-189, a superoxide dismutase-catalase mimetic
Partial volume rat lung irradiation: The protective/mitigating effects of Eukarion-189, a superoxide dismutase-catalase mimetic
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DOI：
10.1016/j.radonc.2006.03.017
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发表时间：
2006-05-01
影响因子：
5.7
通讯作者：
Hill, Richard P.
中科院分区：
文献类型：
--
作者：
Langan, Aimee R.;Khan, Mohammed A.;Hill, Richard P.
背景和目的：本研究的目的是阐明sod -过氧化氢酶模拟物Eukarion-189 （EUK-189）对辐照后大鼠肺DNA损伤的保护/减轻作用。这些研究的重点是辐照后给予EUK-189的疗效（缓解）。患者和方法：我们将雌性Sprague-Dawley大鼠的整个或下肺暴露于剂量从10到20.5 Gy的Co-60伽马射线中。EUK-189处理组的动物在放射后（PI）的不同时间腹腔注射2或30 mg/kg。微核试验用于检测DNA损伤在不同时间，直到16周PI。结果：我们的研究结果表明，辐照后给予EUK-189可有效减少辐射暴露后不同时间肺成纤维细胞微核的形成。然而，在胸部照射后的前3天使用EUK-189治疗并没有改变照射后2-3个月引起严重发病率所需的剂量。结论：Eukarion-189在照射后不久给予的保护表明，在肺部观察到的DNA损伤可能是由放射治疗引发的慢性炎症反应诱导的ROS的慢性产生引起的。我们推测，我们未能在2-3个月观察到对严重发病率的保护，可能是因为我们的治疗方案只阻断了ROS产生的初始波，治疗需要更长的时间来抑制慢性炎症反应的影响。2006爱思唯尔爱尔兰有限公司版权所有。
Background and purpose: The purpose of the current study was to elucidate the protective/mitigating effects of a SOD-catalase mimetic, Eukarion-189 (EUK-189), on DNA damage in rat lung following irradiation. The particular focus of these studies was the efficacy of EUK-189 when given after irradiation (mitigation).Patients and methods: We exposed whole or lower lungs of female Sprague-Dawley rats to doses ranging from 10 to 20.5 Gray (Gy) of Co-60 gamma rays. Animals in the EUK-189 treated groups received 2 or 30 mg/kg intraperitoneally (i.p.) at various times postirradiation (PI). A micronucleus assay was used to examine DNA damage at various times up to 16 weeks PI.Results: Our results indicated that EUK-189 administration after irradiation is effective at reducing micronucleus formation in lung fibroblasts at various times following radiation exposure. Treatment with EUK-189 in the first 3 days after thoracic irradiation did not, however, modify the dose required to cause severe morbidity at 2-3 months after irradiation.Conclusions: The protection produced when Eukarion-189 was given shortly after irradiation suggests that DNA damage observed in the lung may be caused by chronic production of ROS induced by a chronic inflammatory response initiated by the radiation treatment. We speculate that our failure to observe protection against severe morbidity at 2-3 months may be because our treatment regime only blocked the initial wave of ROS production and that treatment needs to be more prolonged to suppress the effects of a chronic inflammatory response. (c) 2006 Elsevier Ireland Ltd. All rights reserved.