Intracellular glutathione and bronchoalveolar cells in fibrosing alveolitis: effects of N-acetylcysteine.
Extracellular glutathione deficiency and exaggerated oxidative stress may contribute to the pathogenesis of fibrosing alveolitis (FA). High-dose N-acetylcysteine (NAC) supplementation partially reverses extracellular glutathione depletion and oxidative damage, but effects on intracellular glutathione are unknown. Intracellular total glutathione (GSHt) and activation of bronchoalveolar lavage cells (BAC) obtained from 18 FA patients (9 males, aged 52+/-2 yrs), before and after 12 weeks of oral NAC (600 mg t.i.d.), were assessed. Eight healthy nonsmokers (2 males, aged 36+/-6 yrs) served as a control group. Intracellular GSHt was decreased in FA (1.57+/-0.20 nmol 1x10(6) BAC(-1) versus 2.78+/-0.43 nmol x 10(6) BAC(-1)). After NAC treatment, the intracellular GSHt content increased (1.57+/-0.20 versus 1.87+/-0.19 nmol x 1 x 10(6) BAC(-1)). The spontaneous oxidative activity of BAC decreased after NAC treatment (2.7+/-0.8 versus 1.0+/-0.2 nmol x 1 x 10(6) BAC(-1) x h(-1)). Interleukin-8 concentration (82.1+/-31.5 versus 80.0+/-22.6 pg x mL bronchoalveolar fluid (BALF), nonsignificant (NS)) and myeloperoxidase activity (1.93+/-0.64 versus 1.55+/-0.47 mU x mL(-1) BALF, NS) did not change significantly, but were found to be inversely correlated to intracellular GSHt. In conclusion, high-dose N-acetylcysteine supplementation increases intracellular glutathione levels slightly. This increase is associated with a mild reduction of oxidative activity but not with a reduction of bronchoalveolar cell activation in these patients.
Behr
J
J
Dept of Internal Medicine, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany. jbehr@med1.med.uni-muenchen.de
Degenkolb
B
B
Krombach
F
F
Vogelmeier
C
C
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology*; D005978:Glutathione / Q000032:analysis* / Q000096:biosynthesis; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000032:analysis; D011446:Prospective Studies; D011658:Pulmonary Fibrosis / Q000503:physiopathology* / Q000628:therapy*
D016166:Free Radical Scavengers; D016209:Interleukin-8; D009195:Peroxidase; D005978:Glutathione; D000111:Acetylcysteine