title: Subcutaneous administration of bovine superoxide dismutase protects lungs from radiation-induced lung injury.
abstract: BACKGROUND
  The objective of the present study was to determine whether single administration of the antioxidant enzyme bovine superoxide dismutase (bSOD) after radiation therapy (RT) mitigates development of pulmonary toxicity in rats.
  
  
  METHODS
  Female F344 rats (n = 60) were divided among six experimental groups: (1) RT, single dose of 21 Gy to the right hemithorax; (2) RT + 5 mg/kg bSOD; (3) RT + 15 mg/kg bSOD; (4) No RT; (5) sham RT + 5 mg/kg bSOD; and (6) sham RT + 15 mg/kg bSOD. A single subcutaneous injection of bSOD (5 or 15 mg/kg) was administered 24 h post-radiation. The effects of bSOD on radiation-induced lung injury were assessed by measurement of body weight, breathing frequency, and histopathological changes. Immunohistochemistry was used to evaluate oxidative stress (8-OHdG(+), NOX4(+), nitrotyrosine(+), and 4HNE(+) cells), macrophage activation (ED1(+)), and expression of profibrotic transforming growth factor-β or TGF-β in irradiated tissue.
  
  
  RESULTS
  Radiation led to an increase in all the evaluated parameters. Treatment with 15 mg/kg bSOD significantly decreased levels of all the evaluated parameters including tissue damage and breathing frequency starting 6 weeks post-radiation. Animals treated with 5 mg/kg bSOD trended toward a suppression of radiation-induced lung damage but did not reach statistical significance.
  
  
  CONCLUSIONS
  The single application of bSOD (15 mg/kg) ameliorates radiation-induced lung injury through suppression of reactive oxygen species/reactive nitrogen species or ROS/RNS-dependent tissue damage.
authors.affiliation: University of Maryland School of Medicine, Department of Radiation Oncology, Division of Translational Radiation Sciences, Baltimore, MD, USA.
authors.forename: Vlado
authors.initials: V
authors.lastname: Antonic
authors.affiliation: Duke University Medical Center, Department of Radiation Oncology, Durham, NC, USA.
authors.forename: Zahid N
authors.initials: ZN
authors.lastname: Rabbani
authors.affiliation: University of Maryland School of Medicine, Department of Radiation Oncology, Division of Translational Radiation Sciences, Baltimore, MD, USA.
authors.forename: Isabel L
authors.initials: IL
authors.lastname: Jackson
authors.affiliation: University of Maryland School of Medicine, Department of Radiation Oncology, Division of Translational Radiation Sciences, Baltimore, MD, USA.
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Vujaskovic
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D002417:Cattle; D003094:Collagen / Q000032:analysis; D005260:Female; D005355:Fibrosis; D007279:Injections, Subcutaneous; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects*; D008262:Macrophage Activation / Q000187:drug effects / Q000528:radiation effects; D008667:Metalloproteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D017564:Radiation Pneumonitis / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D056152:Respiratory Rate / Q000187:drug effects / Q000528:radiation effects; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D008667:Metalloproteins; D011837:Radiation-Protective Agents; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D003094:Collagen; D013482:Superoxide Dismutase; C005180:orgotein
keywords: bovine superoxide dismutase; fibrosis; radiation-induced lung injury; reactive oxygen species