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

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

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

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

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 microg 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-beta1 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.

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

M Machtay,A Scherpereel,J Santiago,J Lee,J McDonough,P Kinniry,E Arguiri,VV Shuvaev,J Sun,K Cengel,CC Solomides,M Christofidou-Solomidou,

For similar enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: p21-activated kinases research abstracts see: enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-serine-threonine kinases: p21-activated kinases research

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

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Radiotherapy and oncology : journal of the Europea

VOLUME: 81

Page Numbers: 196-205

Journal Abbreviation:

ISSN: 0167-8140

DAY: 27

MONTH: 10

YEAR: 2006

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

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LANGUAGE: eng

NlmUniqueID: 8407192

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

KEYWORDS: p21-Activated Kinases

MESH TERMS: genetics

Chemical & Substance for Abstract: Systemic polyethylene glycol-modified (PEGylated) superoxide dismutase and catalase mixture attenuates radiation pulmonary fibrosis in the C57/bl6 mouse. Information

Substance Name: p21-Activated Kinases

Registry Number: EC 2.7.11.1

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

AFFILIATION: Department of Medicine, Pulmonary, Allergy, and Critical Care Division, Thomas Jefferson University Medical Center, Philadelphia, PA 19104, USA.

Country: Ireland

AGENCY: United States NCI

GRANT: R21 CA118111-01

ACRONYM: CA

MEDLINETA: Radiother Oncol

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