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

This study examines the activity of the antioxidant N-acetylcysteine on bleomycin-induced pulmonary fibrosis in rats with emphasis on the early inflammatory phase. Rats receiving N-acetylcysteine (300 mg kg−1 day−1, intraperitoneal) had less augmented lung wet weight, and lower levels of proteins, l...

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Autores: Serrano-Mollar, Anna, Closa, Daniel, Morcillo, Esteban J., Bulbena, Oriol
Tipo de recurso: artículo
Fecha de publicación:2003
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/2971
Acceso en línea:http://hdl.handle.net/10261/2971
Access Level:acceso abierto
Palabra clave:Pulmonary fibrosis
Bleomycin
Rat
N-acetylcysteine
Inflammation
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spelling In vivo antioxidant treatment protects against bleomycin-induced lung damage in ratsSerrano-Mollar, AnnaClosa, DanielMorcillo, Esteban J.Bulbena, OriolPulmonary fibrosisBleomycinRatN-acetylcysteineInflammationThis study examines the activity of the antioxidant N-acetylcysteine on bleomycin-induced pulmonary fibrosis in rats with emphasis on the early inflammatory phase. 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. 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. N-Acetylcysteine suppressed the bleomycin-induced increased activation of lung NF-κB (shift assay and immunohistochemistry), and decreased the augmented levels of the early inflammatory cytokines, tumour necrosis factor-α, interleukin-β, interleukin-6 and macrophage inflammatory protein-2 observed in bronchoalveolar lavage fluid at 1 and 3 days postbleomycin exposure. At 15 days postbleomycin, N-acetylcysteine decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content: 6351±669 and 4626±288 μg 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. 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.This work was supported by Grant 1FD97-1143 from the European Union (Regional Development Funds, FEDER), CICYT (Spanish Government), Regional Government (Generalitat Valenciana) and Grant FIS98/1367 (Spanish Ministry of Health).Peer reviewedWiley-Blackwell200820082003info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501481474 bytesapplication/pdfhttp://hdl.handle.net/10261/2971reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1038/sj.bjp.0705138info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/29712026-05-22T06:33:51Z
dc.title.none.fl_str_mv In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats
title In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats
spellingShingle In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats
Serrano-Mollar, Anna
Pulmonary fibrosis
Bleomycin
Rat
N-acetylcysteine
Inflammation
title_short In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats
title_full In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats
title_fullStr In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats
title_full_unstemmed In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats
title_sort In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats
dc.creator.none.fl_str_mv Serrano-Mollar, Anna
Closa, Daniel
Morcillo, Esteban J.
Bulbena, Oriol
author Serrano-Mollar, Anna
author_facet Serrano-Mollar, Anna
Closa, Daniel
Morcillo, Esteban J.
Bulbena, Oriol
author_role author
author2 Closa, Daniel
Morcillo, Esteban J.
Bulbena, Oriol
author2_role author
author
author
dc.subject.none.fl_str_mv Pulmonary fibrosis
Bleomycin
Rat
N-acetylcysteine
Inflammation
topic Pulmonary fibrosis
Bleomycin
Rat
N-acetylcysteine
Inflammation
description This study examines the activity of the antioxidant N-acetylcysteine on bleomycin-induced pulmonary fibrosis in rats with emphasis on the early inflammatory phase. 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. 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. N-Acetylcysteine suppressed the bleomycin-induced increased activation of lung NF-κB (shift assay and immunohistochemistry), and decreased the augmented levels of the early inflammatory cytokines, tumour necrosis factor-α, interleukin-β, interleukin-6 and macrophage inflammatory protein-2 observed in bronchoalveolar lavage fluid at 1 and 3 days postbleomycin exposure. At 15 days postbleomycin, N-acetylcysteine decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content: 6351±669 and 4626±288 μg 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. 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.
publishDate 2003
dc.date.none.fl_str_mv 2003
2008
2008
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/2971
url http://hdl.handle.net/10261/2971
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1038/sj.bjp.0705138
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv Wiley-Blackwell
publisher.none.fl_str_mv Wiley-Blackwell
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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