title: Intravenous superoxide dismutase administration reduces contralateral lung injury induced by unilateral lung ischemia and reperfusion in rats through suppression of activity and protein expression of matrix metalloproteases.
abstract: BACKGROUND
  Ischemia and reperfusion (I/R) of the lungs induces massive superoxide radical production. On the other hand, matrix metalloproteases (MMPs) were shown to play an essential role in I/R-associated lung injury. We aimed to investigate the lung-protective efficacy of intravenous superoxide dismutase (SOD) administration and its relation with MMPs activity in the lungs subsequent to I/R injury.
  
  
  METHODS
  Twenty-two male Sprague-Dawley rats were divided into a sham group (n = 6), a unilateral lung I/R group (n = 8), and a SOD-treated lung I/R group (n = 8). Unilateral lung ischemia was conducted by occluding the left lung hilum for 90 min, followed by 5 hours of reperfusion through release of the occlusion. In the SOD-treated group, SOD was administered intravenously during the first hour of reperfusion. We assessed the protein contents in the broncho-alveolar lavage fluid (PCBAL) as a marker for protein permeability and lung wet-to-dry weight ratio (W/D) for lung water content. We also measured levels of lipid peroxidation and MMP activity in the lungs, by tissue malonedealdehyde (MDA) level with the use of enzyme-linked immunoassay, and the gelatin zymography technique, respectively.
  
  
  RESULTS
  Forty-eight hours of left-lung I/R significantly increased PCBAL (P < .001), W/D (P < .05), tissue MDA level (P < .05), and MMP-9 and MMP-2 activity. SOD treatment attenuated I/R-induced contralateral lung injury, reducing pulmonary permeability, lipid peroxidation, and MMP activities.
  
  
  CONCLUSIONS
  I/R injury of the left lung induced increases in W/D, PCBAL, MDA level, and MMP-9 activity in the right lung. SOD treatment during the first hour of a 5-hour reperfusion protected the lung through suppressing MMP-9 activity and reducing tissue lipid peroxidation.
authors.affiliation: Division of Chest Medicine, Internal Medicine, Shin Kong Wu-Ho-Su Memorial Hospital, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: D Y-W
authors.initials: DY
authors.lastname: Yeh
authors.affiliation: Division of Emergency Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; Granulate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: S-P
authors.initials: SP
authors.lastname: Tung
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Y H
authors.initials: YH
authors.lastname: Fu
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Y C
authors.initials: YC
authors.lastname: Yang
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. Electronic address: 078625@mail.fju.edu.tw.
authors.forename: J J
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000008:administration & dosage; D007262:Infusions, Intravenous; D055370:Lung Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000008:administration & dosage*
chemical_list: D016166:Free Radical Scavengers; D013482:Superoxide Dismutase; D020782:Matrix Metalloproteinases