title: The protective role of MnTBAP in oxidant-mediated injury and inflammation in a rat model of lung contusion.
abstract: BACKGROUND
  Lung contusion (LC) is a unique direct and focal insult that is considered a major risk factor for the initiation of acute lung injury and acute respiratory distress syndrome. We have shown recently that consumption of nitric oxide (due to excess superoxide) resulting in peroxynitrite formation leads to decreased vascular reactivity after LC. In this study, we set out to determine whether the superoxide scavenger Mn (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) plays a protective role in alleviating acute inflammatory response and injury in LC.
  
  
  METHODS
  Nonlethal, closed-chest, bilateral LC was induced in a rodent model. Administration of the superoxide dismutase mimetic MnTBAP concurrently in LC in rats was performed, and bronchoalveolar lavage (BAL) and lung samples were analyzed for degree of injury and inflammation at 5 and 24 h after the insult. The extent of injury was assessed by the measurement of cells and albumin with cytokine levels in the BAL and lungs. Lung samples were subjected to H&E and superoxide staining with dihydro-ethidium. Protein-bound dityrosine and nitrotyrosine levels were quantified in lung tissue by tandem mass spectrometry.
  
  
  RESULTS
  The degrees of lung injury after LC as determined by BAL albumin levels were significantly decreased in the MnTBAP-administered rats at all the time points when compared to the corresponding controls. The release of proinflammatory cytokines and BAL neutrophils was significantly less in the rats administered MnTBAP after LC. Administration of MnTBAP decreased tissue damage and decreased necrosis and neutrophil-rich exudate at the 24-h time point. Staining for superoxide anions showed significantly greater intensity in the lung samples from the LC group compared to the LC+ MnTBAP group. High-performance liquid chromatography/tandem mass spectrometry revealed that MnTBAP treatment significantly attenuated dityrosine and nitrotyrosine levels, consistent with decreased oxidant injury.
  
  
  CONCLUSIONS
  Superoxide dismutase mimetic-MnTBAP reduced permeability and oxidative injury in LC and may have a therapeutic role in diminishing inflammation in LC.
authors.affiliation: Department of Surgery, University of Michigan.
authors.forename: Madathilparambil V
authors.initials: MV
authors.lastname: Suresh
authors.forename: Bi
authors.initials: B
authors.lastname: Yu
authors.forename: Satyan
authors.initials: S
authors.lastname: Lakshminrusimha
authors.forename: David
authors.initials: D
authors.lastname: Machado-Aranda
authors.forename: Nicholas
authors.initials: N
authors.lastname: Talarico
authors.forename: Lixia
authors.initials: L
authors.lastname: Zeng
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Davidson
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Pennathur
authors.forename: Krishnan
authors.initials: K
authors.lastname: Raghavendran
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D003288:Contusions / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D008297:Male; D008665:Metalloporphyrins / Q000627:therapeutic use*; D016877:Oxidants / Q000633:toxicity*; D051381:Rats; D020318:Rats, Long-Evans; D013481:Superoxides / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D016877:Oxidants; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D013481:Superoxides