Experimental radiotherapySystemic polyethylene glycol-modified (PEGylated) superoxide dismutase and catalase mixture attenuates radiation pulmonary fibrosis in the C57/bl6 mouse☆
Section snippets
Reagents
The following reagents were used in the study: PEG-catalase and PEG-SOD (Cu/Zn-SOD from bovine erythrocytes) from Sigma (St. Louis, MO), Bradford Bio-Rad protein microassay kit from (Bio-Rad Laboratories, Hercules, CA).
Animals
Our studies used female C57/bl6 mice, a strain well characterized in the field of pulmonary radioprotection [18]. Mice were obtained from Charles River (Wilmington, MA). Mice were irradiated at the age of approximately 6–8 weeks in groups of 8 mice per irradiation round. Ten mice
Effect of PEG-SOD and PEG-catalase mixture on acute radiation pneumonitis
C57/bl6 mice develop radiation pneumonitis as early as 3 weeks post single fraction XRT (13.5 GY) (Fig. 1). Systemic PEG-AOE (100 μg/mouse for each PEGylated AOE) given i.v. at the time of radiation did not alleviate lung injury or inflammation as judged by BAL protein levels or BAL neutrophils, respectively, at any time-point investigated (1, 2, 3, 7, 14, 21 and 120 days post XRT).
Effect of AOEs on oxidative modification and apoptosis in irradiated lung tissues
Malondialdehyde (MDA) is a product of lipid peroxidation, which in turn is a result of free radical interactions
Survival
Overall, no statistically significant survival differences were observed between irradiated, PEG-AOE-treated and non-drug treated controls (p = 0.8569). Nevertheless, the overall survival rate at 4 months yielded a sufficient number of animals to allow the semiquantitative and quantitative analysis of the fibrotic status of the lungs in each experiment.
Discussion
These studies provide strong evidence that systemically delivered, non-targeted antioxidant drug therapy (PEG-SOD and PEG-CAT enzymes) can decrease some of the manifestations of radiation pneumonopathy. Specifically, several early molecular events were diminished and the important “late” effect of fibrosis was also reduced. Interestingly, however, the intermediate phase of radiation lung injury – inflammation or pneumonitis – was not affected at all. This supports the hypothesis that
Conflict of interest
The co-authors of this manuscript state that there is no conflict of interest.
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Funded in part by American Cancer Society IRG #78-002-23 (Machtay); National American Lung Association #RG-087-N, National Institute of Health NIH-1R21CA-(118111-01) and University of Pennsylvania Research Foundation (Christofidou-Solomidou).