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Attenuation by oral N-acetylcysteine of bleomycin-induced lung injury in rats

Depts of ¹ Pharmacology, ² Pathology and ⁴ Physiology, University of València, ³ Dept of Medical Bioanalysis, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigacions Cientificas, Barcelona, Spain, Zambon Group Spa, ⁵ Bresso, Italy and ⁶ , Barcelona, Spain

CORRESPONDENCE: J. Morcillo, Dept of Pharmacology, Faculty of Medicine, Av. Blasco Ibanez 15, E-46010, Valencia, Spain. Fax: 34 963864622

Keywords: bleomycin, inflammation, N-acetylcysteine, pulmonary fibrosis, rat

Received: June 5, 2000
Accepted January 25, 2001

The present work was supported by grant 1FD97-1143 from the European Union (Regional Development Funds; FEDER), CICYT (Spanish Government) and Regional Government (Generalitat Valenciana), and a research grant from Zambon Group (Milano, Italy and Barcelona, Spain).

Antioxidant therapy may be useful in diseases with impaired oxidant-antioxidant balance such as pulmonary fibrosis. This study examines the effect of N-acetylcysteine (NAC) on bleomycin-induced lung fibrosis in rats.

NAC (3 mmol·kg^–1; oral) was given daily from 1 week prior to a single intratracheal instillation of bleomycin (2.5 U·kg^–1) or saline, until 14 days postinstillation.

NAC partially decreased the augmented collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,354±386 and 3,416±326 µg·lung^–1 in vehicle-treated and NAC-treated rats, respectively; p<0.05). The histological assessment using a semiquantitative score showed less collagen deposition and inflammatory cells in NAC-treated rats compared to those receiving bleomycin alone. NAC failed to inhibit the bleomycin-induced increases in lung wet weight and in cell counts and protein levels of bronchoalveolar lavage fluid, but significantly increased total glutathione and taurine levels in bronchoalveolar lavage fluid.

These results indicate that oral N-acetylcysteine improves the pulmonary antioxidant protection and may be useful in reducing lung damage produced by bleomycin.

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