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Short-term treatment with a SOD/catalase mimetic, EUK-207, mitigates pneumonitis and fibrosis after single-dose total-body or whole-thoracic irradiation. Radiat Res 2012 Nov;178(5):468-80 PMID: 23020094 PMCID: PMC3678766

Pubmed ID

23020094

Abstract

In the event of a radiological accident or terrorist attack, whole- or partial-body exposure can injure the lungs. To simulate such an incident, we used a single fraction of total-body irradiation (TBI) or whole-thoracic irradiation to induce pneumonitis or pulmonary fibrosis, respectively, in a rat model. The superoxide dismutase and catalase mimetic EUK-207 was given by subcutaneous injection (20 mg/kg/day, 5 days per week, once daily) starting at 7 days after irradiation and stopping before pneumonitis developed. After TBI, morbidity and the increase in breathing rates associated with pneumonitis were significantly improved in rats treated with EUK-207 compared to rats receiving irradiation alone. At 42 days after TBI (the peak of pneumonitis) changes in vascular end points including pulmonary hemodynamics ex vivo and relative arterial density in lungs were also mitigated by EUK-207. At 7 months after whole-thoracic irradiation, EUK-207 reduced synthesis of collagen as assessed by the Sircol collagen assay and Masson's trichrome staining. Our results demonstrate promise for EUK-207 as a mitigator of radiation pneumonitis and fibrosis. We also demonstrate for the first time mitigation of multiple vascular injuries in the irradiated lung in vivo by EUK-207.

Author List

Gao F, Fish BL, Szabo A, Doctrow SR, Kma L, Molthen RC, Moulder JE, Jacobs ER, Medhora M

Authors

Elizabeth R. Jacobs MD Associate Dean, Professor in the Medicine department at Medical College of Wisconsin
Meetha M. Medhora PhD Professor in the Radiation Oncology department at Medical College of Wisconsin
Aniko Szabo PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin




Scopus

2-s2.0-84868613978   9 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Biomimetic Materials
Catalase
Lung
Organometallic Compounds
Radiation Pneumonitis
Radiation-Protective Agents
Rats
Superoxide Dismutase
Thorax
Whole-Body Irradiation
jenkins-FCD Prod-299 9ef562391eceb2b8f95265c767fbba1ce5a52fd6