Enhanced bleomycin-induced pulmonary damage in mice lacking extracellular superoxide dismutase

Free Radic Biol Med. 2003 Oct 1;35(7):763-71. doi: 10.1016/s0891-5849(03)00402-7.


Extracellular superoxide dismutase (EC-SOD) is highly expressed in the extracellular matrix of lung and vascular tissue. Localization of EC-SOD to the matrix of the lung may protect against oxidative tissue damage that leads to pulmonary fibrosis. This study directly examines the protective role of EC-SOD in a bleomycin model of pulmonary fibrosis and the effect of this enzyme on oxidative protein fragmentation. Mice null for ec-sod display a marked increase in lung inflammation at 14 d post-bleomycin treatment as compared to their wild-type counterparts. Hydroxyproline analysis determined that both wild-type and ec-sod null mice display a marked increase in interstitial fibrosis at 14 d post-treatment, and the severity of fibrosis is significantly increased in ec-sod null mice compared to wild-type mice. To determine if the lack of EC-SOD promotes bleomycin-induced oxidative protein modification, 2-pyrrolidone content (as a measure of oxidative protein fragmentation at proline residues) was assessed in lung tissue from treated mice. 2-Pyrrolidone levels in the lung hydrolysates from ec-sod null mice were increased at both 7 and 14 d post-bleomycin treatment as compared to wild-type mice, indicating EC-SOD can inhibit oxidative fragmentation of proteins in this specific model of oxidative stress.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bleomycin / pharmacology*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Collagen Type I / metabolism
  • Disease Models, Animal
  • Extracellular Space / enzymology*
  • Hydroxyproline / analysis
  • Lung / chemistry
  • Lung / drug effects*
  • Lung / enzymology
  • Lung / pathology*
  • Lung Diseases / chemically induced
  • Lung Diseases / enzymology
  • Lung Diseases / pathology
  • Mice
  • Mice, Transgenic
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / enzymology
  • Pulmonary Fibrosis / pathology
  • Pyrrolidinones / analysis
  • Superoxide Dismutase / deficiency*
  • Superoxide Dismutase / metabolism


  • Collagen Type I
  • Pyrrolidinones
  • Bleomycin
  • Superoxide Dismutase
  • 2-pyrrolidone
  • Hydroxyproline