Protection by N-acetylcysteine against pulmonary endothelial cell damage induced by oxidant injury.
The protective effect of N-acetylcysteine (NAC) against oxidant lung injury was investigated in a model of acute immunological alveolitis in the rat. Intrapulmonary immune complex deposition into rat lungs, induced by intratracheal infusion of immunoglobulin G (IgG) anti-bovine serum albumin (BSA) antibodies and intravenous injection of the antigen, caused lung damage associated with a marked decrease in [14C]5-hydroxytryptamine ([14C]5HT) uptake capacity, taken as a biochemical marker of endothelial cell function. The oral administration of a single dose of NAC (2 mmol.kg-1) 60 min before antigen/antibody (Ag/Ab) treatment was effective in preventing pulmonary endothelial cell [14C]5HT uptake loss induced by immune complex deposition. The mechanisms involved in this lung protective action of NAC were investigated by studying the antioxidant activity of NAC on hypoxanthine/xanthine oxidase-induced lung damage in vitro, and the effectiveness of the drug as lung glutathione (reduced form) (GSH) precursor in diethylmaleate-depleted rats. The results obtained provide further evidence on the ability of NAC to reduce the susceptibility of lung tissue to free radical-induced damage, by potentiating the antioxidant defence systems.
Sala
R
R
Zambon Research S.p.A., Bresso, Milan, Italy.
Moriggi
E
E
Corvasce
G
G
Morelli
D
D
D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000542:Alveolitis, Extrinsic Allergic / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D004727:Endothelium / Q000378:metabolism; D016166:Free Radical Scavengers; D005978:Glutathione / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000009:adverse effects*; D012701:Serotonin / Q000378:metabolism
D000936:Antigen-Antibody Complex; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D012701:Serotonin; D005978:Glutathione; D000111:Acetylcysteine