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Protection Against Pulmonary Injury after Exposure to Blast by N‐Acetylcysteine Amide
Author(s) -
Chavko Mikulas,
Adeeb Saleena,
Ahlers Stephen T.,
McCarron Richard M.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.753.4
Subject(s) - ards , medicine , lung , chemokine , immunology , myeloperoxidase , acetylcysteine , anesthesia , inflammation , andrology , pharmacology , chemistry , antioxidant , biochemistry
Lung contusion is a common problem from blunt chest trauma caused by mechanical forces and by exposure to blast overpressure, often with fatal consequences. Lung contusion is also a risk factor for the development of pneumonia and severe clinical acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Infiltrating neutrophils are considered to be central mediators of lung injuries after blunt trauma. The purpose of this study was to examine the effect of the antioxidant N‐acetylcysteine amide (NACA, ThiolTech, NY) on progression of lung inflammation after exposure to a moderate level of blast overpressure 140 kPa. Rats were administered with NACA (i.p.100 mg/kg) or placebo (PBS) 30 and 60 min after exposure and then 24 h later. Non‐blasted sham‐injected animals served as controls. Myeloperoxidase (MPO) activity in the lung was significantly increased 2 days after blast and returned to controls at 8 days. This increase corresponded with activation of CD11b mRNA and lung inflammatory chemokine mRNA expression (MIP‐1, MCP‐1, and CINC‐1). At 8 days, all inflammatory mediators returned to control levels. In addition, expression of heme oxygenase‐1 (HO‐1) mRNA increased at 2 days after exposure. NACA significantly reduced infiltration of neutrophil and CD11b mRNA activation in lungs, and completely blocked activation of MIP‐1, MCP‐1 and CINC‐1 mRNA. The relatively higher inhibition of chemokine mRNAs compared with reduction in MPO activity and CD11b is in accordance with an antioxidant effect of NACA on reactive oxygen species (ROS) accumulation, rather than by an effect on neutrophil sequestration. The inhibition of HO‐1 mRNA activation after blast was likely also related to the drug antioxidant effect. This work was supported by Office of Naval Research Work Unit 601153N.04508.518.A0406.