PMID- 19174737
OWN - NLM
STAT- MEDLINE
DCOM- 20091228
LR  - 20220311
IS  - 1540-0514 (Electronic)
IS  - 1073-2322 (Linking)
VI  - 32
IP  - 3
DP  - 2009 Sep
TI  - Attenuation of pulmonary inflammation after exposure to blast overpressure by 
      N-acetylcysteine amide.
PG  - 325-31
LID - 10.1097/SHK.0b013e31819c38f1 [doi]
AB  - 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, 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. Recent studies have demonstrated that antioxidants reduced 
      pulmonary inflammation in different models of lung damage. This study examined 
      the effect of antioxidant N-acetylcysteine amide (NACA) on the 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, 60 
      min and 24 h after exposure. Nonblasted sham-injected animals served as controls. 
      Neutrophil infiltration measured by myeloperoxidase (MPO) activity in the lung 
      was significantly increased at 2 days after blast and returned to controls at 8 
      days. This increase corresponded with activation of integrin CD11b mRNA and lung 
      inflammatory chemokine mRNA expression; macrophage inflammatory protein-1 
      (MIP-1), monocyte chemotactic peptide-1 (MCP-1), and cytokine-induced neutrophil 
      chemoattractant-1 (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. No changes were detected in the lung manganase 
      superoxide dismutase (MnSOD) or glutathione reductase (GR) mRNA expression after 
      blast. N-Acetylcysteine amide significantly reduced infiltration of neutrophils 
      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.
FAU - Chavko, Mikulas
AU  - Chavko M
AD  - Trauma and Resuscitative Medicine Department, Naval Medical Research Center, 
      Silver Spring, MD 20910-7500, USA. Mikulas.Chavko@med.navy.mil
FAU - Adeeb, Saleena
AU  - Adeeb S
FAU - Ahlers, Stephen T
AU  - Ahlers ST
FAU - McCarron, Richard M
AU  - McCarron RM
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Antioxidants)
RN  - 0 (CD11b Antigen)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL1)
RN  - 0 (Cxcl1 protein, rat)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 4N69717RKW (N-Acetylcysteinamide)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.8.1.7 (Glutathione Reductase)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*analogs & derivatives/therapeutic use
MH  - Animals
MH  - Antioxidants/*therapeutic use
MH  - CD11b Antigen/genetics
MH  - Chemokine CCL2/genetics
MH  - Chemokine CXCL1/genetics
MH  - Glutathione Reductase/genetics
MH  - Heme Oxygenase-1/metabolism
MH  - Lung Injury/*drug therapy/*immunology/metabolism/pathology
MH  - Macrophage Inflammatory Proteins/genetics
MH  - Male
MH  - Neutrophil Infiltration/immunology/physiology
MH  - Peroxidase/metabolism
MH  - Pneumonia/*drug therapy/*immunology/metabolism/pathology
MH  - Polymerase Chain Reaction
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Superoxide Dismutase/genetics
EDAT- 2009/01/29 09:00
MHDA- 2009/12/29 06:00
CRDT- 2009/01/29 09:00
PHST- 2009/01/29 09:00 [entrez]
PHST- 2009/01/29 09:00 [pubmed]
PHST- 2009/12/29 06:00 [medline]
AID - 10.1097/SHK.0b013e31819c38f1 [doi]
PST - ppublish
SO  - Shock. 2009 Sep;32(3):325-31. doi: 10.1097/SHK.0b013e31819c38f1.