RT Journal Article SR Electronic T1 Oral N‐acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 900 OP 905 DO 10.1183/09031936.03.00018003 VO 22 IS 6 A1 M. Mata A1 A. Ruíz A1 M. Cerdá A1 M. Martinez-Losa A1 J. Cortijo A1 F. Santangelo A1 A. Serrano-Mollar A1 A. Llombart-Bosch A1 E.J. Morcillo YR 2003 UL http://erj.ersjournals.com/content/22/6/900.abstract AB 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‐α 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. 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. 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).