[N-acetylcysteine decreases functional and structural, ARDS-typical lung changes in endotoxin-treated rats].
Oxygen radicals and oxygen radical mediators derived from activated granulocytes are important components in the development of acute lung injury, namely the adult respiratory distress syndrome ARDS. N-acetylcysteine (NAC) is one important substance for endogenous production of reduced glutathion, which is known to be an intra- and extracellular reducing agent also found in lung tissue. We evaluated the effect of exogenous NAC on the endotoxin induced development and course of ARDS in rats. ARDS-like injury was induced in rats via intraperitoneal injection of Salmonella enteritidis endotoxin 30 mg/kg body weight. NAC or solvent was injected intraperitoneally 30 min prior to, at the time of and 30 min after injection of endotoxin respectively with 150 mg/kg body weight each dose. Endotoxin injection in rats resulted in 80% mortality within 72 hours, increased lung wet weight, severe ultrastructural lung damage as measured by histological methods. In isolated, ventilated, with physiological salt solution perfused rat lungs vasocontractility was severely blunted, lung albumin leakage was increased, thromboxane B2 (TXB2) and 6-keto-prostaglandin-F1 alpha (6-keto-PGF1 alpha) perfusate levels were increased. NAC treatment significantly improved survival of endotoxin treated rats, ameliorated structural lung damage, diminished lung wet weight and lung albumin leakage, lowered lung perfusate TXB2 and 6-keto-PGF1 alpha levels and slightly improved vasocontractility in isolated perfused lungs. Therefore, NAC significantly ameliorates ARDS-like lung injury in rats, when given in vivo.
Zentrum für Innere Medizin, Philipps-Universität Marburg.
C O
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Feddersen
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P
Barth
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Püchner
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von Wichert
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D008168:Lung / Q000473:pathology; D010477:Perfusion; D051381:Rats; D017382:Reactive Oxygen Species; D012128:Respiratory Distress Syndrome / Q000473:pathology*; D012477:Salmonella enteritidis; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects*
D004731:Endotoxins; D017382:Reactive Oxygen Species; D000111:Acetylcysteine
N-Acetylcystein vermindert funktionelle und strukturelle, ARDS-typische Lungenschädigungen bei endotoxinbehandelten Ratten.