In vivo antioxidant treatment protects against bleomycin-induced
lung damage in rats.
Serrano-Mollar A, Closa D, Prats N, Blesa S, Martinez-Losa M, Cortijo J,
Estrela JM, Morcillo EJ, Bulbena O.
Department of Medical Bioanalysis, Instituto de Investigaciones Biomedicas de
Barcelona (IIBB-IDIBAPS), CSIC, Barcelona, Spain. Department of Animal
Pathology, Veterinary School, Universitat Autonoma de Barcelona, Bellaterra,
Spain. Pharmacology Department, Faculty of Medicine, Universitat de Valencia,
Valencia, Spain. Physiology Department, Faculty of Medicine, Universitat de
Valencia, Valencia, Spain.
1 This study examines the activity of the antioxidant N-acetylcysteine on
bleomycin-induced pulmonary fibrosis in rats with emphasis on the early
inflammatory phase. 2 Rats receiving N-acetylcysteine (300 mg kg(-1) day(-1),
intraperitoneal) had less augmented lung wet weight, and lower levels of
proteins, lactate dehydrogenase, neutrophil and macrophage counts in
bronchoalveolar lavage fluid and lung myeloperoxidase activity with a betterment
of histological score at 3 days postbleomycin. 3 A diminished lung GSH/GSSG
ratio and augmented lipid hydroperoxides were observed 3 days postbleomycin.
These changes were attenuated by N-acetylcysteine. Alveolar macrophages from
bleomycin-exposed rats released augmented amounts of superoxide anion and nitric
oxide. N-Acetylcysteine did not modify superoxide anion generation but reduced
the increased production of nitric oxide. 4 N-Acetylcysteine suppressed the
bleomycin-induced increased activation of lung NF-kappaB (shift assay and
immunohistochemistry), and decreased the augmented levels of the early
inflammatory cytokines, tumour necrosis factor-alpha, interleukin-beta,
interleukin-6 and macrophage inflammatory protein-2 observed in bronchoalveolar
lavage fluid at 1 and 3 days postbleomycin exposure. 5 At 15 days postbleomycin,
N-acetylcysteine decreased collagen deposition in bleomycin-exposed rats (hydroxyproline
content: 6351+/-669 and 4626+/-288 micro g per lung in drug vehicle- and N-acetylcysteine-treated
rats, respectively; P<0.05). Semiquantitative histological assessment at this
stage showed less collagen deposition in N-acetylcysteine-treated rats compared
to those receiving bleomycin alone. 6 These results indicate that N-acetylcysteine
reduces the primary inflammatory events, thus preventing cellular damage and the
subsequent development of pulmonary fibrosis in the bleomycin rat model. British
Journal of Pharmacology (2003) 138, 1037-1048. doi:10.1038/sj.bjp.0705138
