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PMID: 12684259 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats.

British journal of pharmacology ·Vol. 138 ·No. 6 ·2003-03-00 ·Pages 1037-48

Serrano-Mollar A, Closa D, Prats N, Blesa S, Martinez-Losa M, Cortijo J, Estrela JM, Morcillo EJ, Bulbena O

Abstract

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.

MeSH Terms
Acetonitriles/pharmacology Acetylcysteine/pharmacology,therapeutic use Animals Antioxidants/therapeutic use Biomarkers Bleomycin/adverse effects,analogs & derivatives Bronchoalveolar Lavage Fluid/chemistry,cytology Disease Models, Animal Hydroxyproline/metabolism Immunohistochemistry Lung/drug effects,pathology Macrophages, Alveolar/chemistry,cytology,drug effects Male NF-kappa B/metabolism Organ Size/drug effects Oxidative Stress/drug effects Pneumonia/chemically induced Pulmonary Fibrosis/chemically induced Rats Rats, Sprague-Dawley Reactive Oxygen Species/chemistry,metabolism Time Factors Trityl Compounds/pharmacology
Chemicals
2-(2-chlorophenyl)-2,2-diphenyl acetonitrile Acetonitriles Antioxidants Biomarkers NF-kappa B Reactive Oxygen Species Trityl Compounds Bleomycin bleomycetin Hydroxyproline Acetylcysteine
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Serrano-Mollar A
Department of Medical Bioanalysis, Instituto de Investigaciones Biomédicas de Barcelona (IIBB-IDIBAPS), CSIC, Barcelona, Spain.
Closa D
Prats N
Blesa S
Martinez-Losa M
Cortijo J
Estrela J M
Morcillo E J
Bulbena O
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1038/sj.bjp.0705138
Published
2003-03-00
Pages
1037-48
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1573750
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjp.0705138 PMC Full Text View journal details
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