Systemic polyethylene glycol-modified (PEGylated) superoxide dismutase and catalase mixture attenuates radiation pulmonary fibrosis in the C57/bl6 mouse

Mitchell Machtay, Arnaud Scherpereel, José Santiago, James Lee, Jim McDonough, Paul Kinniry, Evguenia Arguiri, Vladimir V. Shuvaev, Jing Sun, Keith Cengel, Charalambos C. Solomides, Melpo Christofidou-Solomidou

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Purpose: Since oxidative injury is implicated in radiation-induced tissue damage to the lung, we studied systemically administered polyethylene glycol (PEGylated) antioxidant enzymes (AOEs) as pulmonary radioprotectors in mice. Methods and materials: C57/bl6 Mice received 13.5 Gy single-dose irradiation to the thorax. One cohort also received 100 μg of a 1:1 mixture of PEG-AOEs {PEG-catalase and PEG-superoxide dismutase (SOD)} intravenously, pre-irradiation and subgroups were evaluated at variable time-points for inflammation and fibrosis. Potential for AOE tumor protection was studied by thoracic irradiation of mice with Lewis lung carcinoma. Results: At 48 h post-irradiation, control irradiated mice had marked elevations of tissue p21, Bax and TGF-β1 in lungs, not seen in irradiated, PEG-AOE-treated mice. TUNEL staining of lung sections was performed at just one time-point (24 h post-irradiation) and revealed a decrease in apoptotic cells with AOE treatment. At four months post-irradiation, these mice had significantly increased pulmonary fibrosis as measured by hydroxyproline content. Mice treated with PEG-AOE prior to irradiation had 4-month hydroxyproline levels that were similar to that of unirradiated controls (p = 0.28). This corresponded to less pulmonary fibrosis as visualized histologically when compared with mice irradiated without AOEs. PEG-AOEs did not prevent post-irradiation pulmonary inflammation or lung cancer response to irradiation. Conclusions: A mixture of PEG-SOD and PEG-CAT successfully diminished radiation pulmonary fibrosis in mice. There was also a corresponding effect on several early biomarkers of lung injury and decreased apoptosis. There were no significant effects on acute pneumonitis or tumor protection.

Original languageEnglish (US)
Pages (from-to)196-205
Number of pages10
JournalRadiotherapy and Oncology
Volume81
Issue number2
DOIs
StatePublished - Nov 2006

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'Systemic polyethylene glycol-modified (PEGylated) superoxide dismutase and catalase mixture attenuates radiation pulmonary fibrosis in the C57/bl6 mouse'. Together they form a unique fingerprint.

Cite this