2: Br J Pharmacol 2003 Mar;138(6):1037-1048  

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

PMID: 12684259




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