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Antioxidants 2018, 7(3), 40; https://doi.org/10.3390/antiox7030040

Post-Irradiation Treatment with a Superoxide Dismutase Mimic, MnTnHex-2-PyP5+, Mitigates Radiation Injury in the Lungs of Non-Human Primates after Whole-Thorax Exposure to Ionizing Radiation

1
Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040, USA
2
Department of Radiation Oncology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040, USA
3
Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Frederick, MD 21702, USA
4
Department of Biomedical Engineering, Wake Forest University School of Medicine, Biotech Place, 575 N. Patterson Ave., Winston-Salem, NC 21701, USA
5
Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27708, USA
6
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27708, USA
7
Department of Medicine Duke University Medical Center, Durham, NC 27708, USA
8
Duke Cancer Institute, Pharmaceutical Research Shared Resource, PK/PD Core Laboratory, Duke University Medical Center, Durham, NC 27708, USA
9
Department of Radiation Oncology, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA
*
Author to whom correspondence should be addressed.
Received: 29 January 2018 / Revised: 23 February 2018 / Accepted: 27 February 2018 / Published: 7 March 2018
(This article belongs to the Special Issue Superoxide Dismutase (SOD) Enzymes, Mimetics and Oxygen Radicals)
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Abstract

Radiation injury to the lung is the result of acute and chronic free radical formation, and there are currently few effective means of mitigating such injury. Studies in rodents indicate that superoxide dismutase mimetics may be effective in this regard; however, studies in humans or large animals are lacking. We hypothesized that post-exposure treatment with the lipophilic mitochondrial superoxide dismutase mimetic, MnTnHex-2-PyP5+ (hexyl), would reduce radiation-induced pneumonitis and fibrosis in the lungs of nonhuman primates. Rhesus monkeys (Macaca mulatta) received 10 Gy whole thorax irradiation, 10 Gy + hexyl treatment, sham irradiation, or sham irradiation + hexyl. Hexyl was given twice daily, subcutaneously, at 0.05 mg/kg, for 2 months. Animals were monitored daily, and respiratory rates, pulse oximetry, hematology and serum chemistry panels were performed weekly. Computed tomography scans were performed at 0, 2, and 4 months after irradiation. Supportive fluid therapy, corticosteroids, analgesics, and antibiotics were given as needed. All animals were humanely euthanized 4.5 months after irradiation, and pathologic assessments were made. Multifocal, progressive lung lesions were seen at 2 and 4 months in both irradiated groups. Hexyl treatment delayed the onset of radiation-induced lung lesions, reduced elevations of respiratory rate, and reduced pathologic increases in lung weight. No adverse effects of hexyl treatment were found. These results demonstrate (1) development of a nonhuman primate model of radiation-induced lung injury, (2) a significant mitigating effect of hexyl treatment on lung pathology in this model, and (3) no evidence for toxicity of hexyl at the dose studied. View Full-Text
Keywords: superoxide dismutase mimetic; MnTnHex-2-PyP5+; irradiation; Macaca mulatta; lung injury superoxide dismutase mimetic; MnTnHex-2-PyP5+; irradiation; Macaca mulatta; lung injury
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Cline, J.M.; Dugan, G.; Bourland, J.D.; Perry, D.L.; Stitzel, J.D.; Weaver, A.A.; Jiang, C.; Tovmasyan, A.; Owzar, K.; Spasojevic, I.; Batinic-Haberle, I.; Vujaskovic, Z. Post-Irradiation Treatment with a Superoxide Dismutase Mimic, MnTnHex-2-PyP5+, Mitigates Radiation Injury in the Lungs of Non-Human Primates after Whole-Thorax Exposure to Ionizing Radiation. Antioxidants 2018, 7, 40.

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