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2 May 2016 Cerium Oxide Nanoparticles: A Potential Medical Countermeasure to Mitigate Radiation-Induced Lung Injury in CBA/J Mice
P-T. Xu, B. W. Maidment, V. Antonic, I. L. Jackson, S. Das,, A. Zodda, X. Zhang, S. Seal, Z. Vujaskovic
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Abstract

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.

P-T. Xu, B. W. Maidment, V. Antonic, I. L. Jackson, S. Das,, A. Zodda, X. Zhang, S. Seal, and Z. Vujaskovic "Cerium Oxide Nanoparticles: A Potential Medical Countermeasure to Mitigate Radiation-Induced Lung Injury in CBA/J Mice," Radiation Research 185(5), 516-526, (2 May 2016). https://doi.org/10.1667/RR14261.1
Received: 10 September 2015; Accepted: 1 March 2016; Published: 2 May 2016
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