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Intracellular glutathione and bronchoalveolar cells in fibrosing alveolitis: effects of N-acetylcysteine

¹ Dept of Internal Medicine, Division for Pulmonary Diseases, and ² Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany

CORRESPONDENCE: J. Behr, Department of Internal Medicine I, Division for Pulmonary Diseases, Klinikum Grosshadern, University of Munich, Marchioninistr. 15, 81377, Munich, Germany. Fax: 49 8970958877. E-mail: jbehr@med1.med.uni-muenchen.de

Keywords: fibrosing alveolitis, glutathione, interleukin-8, myeloperoxidase, oxidative activity

Received: January 15, 2001
Accepted November 2, 2001

J. Behr was supported by Wilhelm Sander-Stiftung

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 (GSH_t) 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 GSH_t was decreased in FA (1.57±0.20 nmol·1x10⁶ BAC^–1 versus 2.78±0.43 nmol·10⁶ BAC^–1). After NAC treatment, the intracellular GSH_t content increased (1.57±0.20 versus 1.87±0.19 nmol·1x10⁶ BAC^–1). The spontaneous oxidative activity of BAC decreased after NAC treatment (2.7±0.8 versus 1.0±0.2 nmol·1x10⁶ BAC^–1·h^–1). Interleukin-8 concentration (82.1±31.5 versus 80.0±22.6 pg·mL bronchoalveolar fluid (BALF), nonsignificant (ns)) and myeloperoxidase activity (1.93±0.64 versus 1.55±0.47 mU·mL^–1 BALF, ns) did not change significantly, but were found to be inversely correlated to intracellular GSH_t.

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.

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