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Depts of 1 Pharmacology and 2 Pathology, Faculty of Medicine, University of Valencia, and 4 Dept of Medical Bioanalysis, Institute of Biomedical Research of Barcelona (IIBB-IDIBAPS), CSIC, Barcelona, Spain. 3 Zambon Group Spa, Bresso (Milan), Italy
CORRESPONDENCE: E.J. Morcillo, Dept of Pharmacology, Faculty of Medicine, 15 Av. Blasco Ibanez, E-46010, Valencia, Spain. Fax: 34 963864622. E-mail: Esteban.Morcillo@uv.es
Keywords: bleomycin, Muc5ac, N-acetylcysteine, pulmonary fibrosis, rat
Received: February 17, 2003
Accepted July 22, 2003
The present work was supported by research grants SAF2000-0144 and SAF2002-04667 from CICYT (Ministry of Science and Technology, Spain) and from Zambon Spa (Italy).
Oxidative stress is involved in the pathogenesis of pulmonary fibrosis, therefore antioxidants may be of therapeutic value. Clinical work indicates that N-acetylcysteine (NAC) may be beneficial in this disease. The activity of this antioxidant was examined on bleomycin-induced lung damage, mucus secretory cells hyperplasia and mucin Muc5ac gene expression in rats.
NAC (3 mmol·kg–1·day–1) or saline was given orally to Sprague-Dawley rats for 1 week prior to a single intratracheal instillation of bleomycin (2.5 U·kg–1) and for 14 days postinstillation.
NAC decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,257±323 and 3,200±192 µg·lung–1 in vehicle- and NAC-treated rats, respectively) and lessened the fibrotic area assessed by morphometric analysis. The bleomycin-induced increases in lung tumour necrosis factor-
These results indicate that bleomycin increases the number of airway secretory cells and their mucin production, and that oral N-acetylcysteine improved pulmonary lesions and reduced the mucus hypersecretion in the bleomycin rat model.
and myeloperoxidase activity were reduced by NAC treatment. The numbers of mucus secretory cells in airway epithelium, and the Muc5ac messenger ribonucleic acid and protein expression, were markedly augmented in rats exposed to bleomycin. These changes were significantly reduced in NAC-treated rats.
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