N-Acetyl Cysteine Attenuates Acute Lung Injury in the Rat

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Authors
  1. Davreux, C.J.
  2. Soric, I.
  3. Nathens, A.B.
  4. Watson, R.W.G.
  5. McGilvray, I.D.
  6. Suntres, Z.E.
  7. Shek, P.N.
  8. Rostein, O.D.
Corporate Authors
Defence R&D Canada - Toronto, Toronto ONT (CAN)
Abstract
The development of the adult respiratory distress syndrome (ARDS) in the critically ill patient is associated with a significant morbidity and mortality. The pulmonary dysfunction in ARDS is largely secondary to neutrophil-mediated oxidant injury. The purpose of these studies is to examine the effect of the antioxidant N-Acetyl cystein (NAC) on a rodent model of lung injury. We postulated that NAC might attenuate lung injury following intratracheal challenge with endotoxin (lipopolysaccharide; LPS). Male Sprague-Dawley rats were administered NAC systemically either before or after intratracheal administration of LPS. Lung injury was assessed by measuring the transpulmonary leakage of 125l-labeled albumin, pulmonary myeloperoxidase content, bronchoalveolar lavage fluid cell counts, pulmonary lipid peroxidation and histology. NAC admininstration significantly attenuated the LPS-induced increases in lung permeability (LPS: .24 ±.08 vs. LPS + NAC: .12 ± .03, p < .05) and reduced the LPS-dependent increase in lipid peroxidation. However, total and differentialBronchoalveolar lavage cell counts and myeloperoxidase content were not affected by NAC pretreatment. Although neutrophil influx was unaffected, neutrophil activation as assessed by surface CD11b expression and chemiluminescence was significantly down-regulated by NAC. Importantly, NAC administration up to 2 h after endotoxin challenge was still able to significantly ameliorate LPS-induced lung injury. Our data suggests tha
Keywords
N-Acetyl Cysteine;Lung Injury;Adult Respiratory Distress Syndrome;Neutrophil Activation;Pulmonary toxicity
Report Number
DRDC-TORONTO-SL-2002-211 — Scientific Literature
Date of publication
01 Dec 1997
Number of Pages
10
DSTKIM No
CA024144
CANDIS No
521649
Format(s):
CD ROM

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