title: Short-term treatment with a SOD/catalase mimetic, EUK-207, mitigates pneumonitis and fibrosis after single-dose total-body or whole-thoracic irradiation.
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.
authors.affiliation: Departments of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Brian L
authors.initials: BL
authors.lastname: Fish
authors.forename: Aniko
authors.initials: A
authors.lastname: Szabo
authors.forename: Susan R
authors.initials: SR
authors.lastname: Doctrow
authors.forename: Lakhan
authors.initials: L
authors.lastname: Kma
authors.forename: Robert C
authors.initials: RC
authors.lastname: Molthen
authors.forename: John E
authors.initials: JE
authors.lastname: Moulder
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Jacobs
authors.forename: Meetha
authors.initials: M
authors.lastname: Medhora
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000008:administration & dosage*; D002374:Catalase / Q000737:chemistry; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D009942:Organometallic Compounds / Q000008:administration & dosage*; D017564:Radiation Pneumonitis / Q000188:drug therapy* / Q000473:pathology; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D051381:Rats; D013482:Superoxide Dismutase / Q000737:chemistry; D013909:Thorax / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D014916:Whole-Body Irradiation
chemical_list: C476761:EUK 207; D009942:Organometallic Compounds; D011837:Radiation-Protective Agents; D002374:Catalase; D013482:Superoxide Dismutase