N-ACETYLCYSTEINE DIMINISHES STRUCTURAL AND FUNCTIONAL LUNG INJURY IN ENDOTOXIN-TREATED RATS

Oxygen radicals and oxygen radical mediators derived from activated gr anulocytes are important components in the developoment of acute lung injury, namely the adult respiratory distress syndrome ARDS. N-acetylc ysteine (NAC) is one important substance for endogenous production of reduced glutathion, which is known to be an intra- and extracellular r educing agent also found in lung tissue. We evaluated the effect of ex ogenous NAC on the endotoxin induced development and course of ARDS in rats. ARDS-like injury was induced in rats via intraperitoneal inject ion of Salmonella enteritidis endotoxin 30 mg/kg body weight. NAC or s olvent was injected intraperitoneally 30 min prior to, at the dme of a nd 30 min after injection of endotoxin respectively with 150 mg/kg bod y weight each dose. Endotoxin injection in rats resulted in 80% mortal ity within 72 hours, increased lung wet weight, severe ultrastructural lung damage as measured by histological methods. In isolated, ventila ted, with physiological salt solution perfused rat lungs vasocontracti lity was severely blunted, lung albumin leakage was increased, thrombo xane B2 (TXB2) and 6-keto-prostaglandin-F1alpha (6-keto-PGF1alpha) per fusate levels were increased. NAC treatment significantly improved sur vival of endotoxin treated rats, ameliorated structural lung damage, d iminished lung wet weight and lung albumin leakage, lowered lung perfu sate TXB2 and 6-keto-PGF1alpha levels and slightly improved vasocontra ctility in isolated perfused lungs. Therefore, NAC significantly ameli orates ARDS-like lung injury in rats, when given in vivo.