Cerium Oxide Nanoparticles: A Potential Medical Countermeasure to Mitigate Radiation-Induced Lung Injury in CBA/J Mice.
Cerium Oxide Nanoparticles: A Potential Medical Countermeasure to Mitigate Radiation-Induced Lung Injury in CBA/J Mice.
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DOI：
10.1667/rr14261.1
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发表时间：
2016-05
影响因子：
3.4
通讯作者：
Vujaskovic Z
中科院分区：
文献类型：
--
作者：
Xu PT;Maidment BW 3rd;Antonic V;Jackson IL;Das S;Zodda A;Zhang X;Seal S;Vujaskovic Z
氧化铈纳米颗粒（CNPs）具有独特的表面再生性能，可以有效地控制活性氧/氮物种。为了确定用CNP治疗是否可以减轻急性辐射暴露后肺损伤的延迟效应，将CBA/J小鼠暴露于15戈伊全胸辐射。从放射后2小时开始，用纳米颗粒、CNP-18和CNP-ME治疗动物，每周两次通过腹膜内注射递送，持续4周，或单独接受放射治疗。在研究的160天终点时，90%接受高剂量（10 μ M）CNP-18治疗的辐照小鼠存活，而仅接受辐射的小鼠存活率为10%（P <0.0001），低剂量（100 nM）CNP-18为30%。低剂量和高剂量CNP-ME治疗的辐射小鼠的存活率均增加了40%，而单独辐射组的存活率为10%。通过流动通气全身体积描记术记录的多个肺功能参数表明，高剂量CNP-18治疗对致死剂量辐射诱导的肺损伤具有显著的辐射保护作用。肺组织学显示，与仅接受辐照的小鼠相比，接受高剂量CNP-18处理的小鼠的结构损伤和胶原沉积显著降低（P <0.0001）。此外，与单独辐照的小鼠相比，在高剂量CNP-18处理组中观察到炎症反应（P <0.01）和血管损伤（P <0.01）显著降低。总之，这项临床前疗效研究的结果清楚地表明，CNP对致死剂量辐射诱导的肺损伤具有临床和组织学显著的缓解和保护作用。
Cerium oxide nanoparticles (CNPs) have a unique surface regenerative property and can efficiently control reactive oxygen/nitrogen species. To determine whether treatment with CNPs can mitigate the delayed effects of lung injury after acute radiation exposure, CBA/J mice were exposed to 15 Gy whole-thorax radiation. The animals were either treated with nanoparticles, CNP-18 and CNP-ME, delivered by intraperitoneal injection twice weekly for 4 weeks starting 2 h postirradiation or received radiation treatment alone. At the study’s end point of 160 days, 90% of the irradiated mice treated with high-dose (10 μM) CNP-18 survived, compared to 10% of mice in the radiation-alone (P < 0.0001) and 30% in the low-dose (100 nM) CNP-18. Both low- and high-dose CNP-ME-treated irradiated mice showed increased survival rates of 40% compared to 10% in the radiation-alone group. Multiple lung functional parameters recorded by flow-ventilated whole-body plethysmography demonstrated that high-dose CNP-18 treatment had a significant radioprotective effect on lethal dose radiation-induced lung injury. Lung histology revealed a significant decrease (P < 0.0001) in structural damage and collagen deposition in mice treated with high-dose CNP-18 compared to the irradiated-alone mice. In addition, significant reductions in inflammatory response (P < 0.01) and vascular damage (P < 0.01) were observed in the high-dose CNP-18-treated group compared to irradiated-alone mice. Together, the findings from this preclinical efficacy study clearly demonstrate that CNPs have both clinically and histologically significant mitigating and protective effects on lethal dose radiation-induced lung injury.