| dc.creator |
Serrano-Mollar, Anna |
|
| dc.creator |
Closa, Daniel |
|
| dc.creator |
Morcillo, Esteban J. |
|
| dc.creator |
Bulbena, Oriol |
|
| dc.date |
2008-02-18T18:03:08Z |
|
| dc.date |
2008-02-18T18:03:08Z |
|
| dc.date |
2003-03-26 |
|
| dc.date.accessioned |
2017-01-31T01:00:10Z |
|
| dc.date.available |
2017-01-31T01:00:10Z |
|
| dc.identifier |
British Journal of Pharmacology 138(6): 1037–1048 (2003) |
|
| dc.identifier |
0007-1188 |
|
| dc.identifier |
http://hdl.handle.net/10261/2971 |
|
| dc.identifier |
10.1038/sj.bjp.0705138 |
|
| dc.identifier.uri |
http://dspace.mediu.edu.my:8181/xmlui/handle/10261/2971 |
|
| dc.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. |
|
| dc.description |
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). |
|
| dc.description |
Peer reviewed |
|
| dc.format |
481474 bytes |
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| dc.format |
application/pdf |
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| dc.language |
eng |
|
| dc.publisher |
Wiley-Blackwell |
|
| dc.relation |
http://dx.doi.org/10.1038/sj.bjp.0705138 |
|
| dc.rights |
openAccess |
|
| dc.subject |
Pulmonary fibrosis |
|
| dc.subject |
Bleomycin |
|
| dc.subject |
Rat |
|
| dc.subject |
N-acetylcysteine |
|
| dc.subject |
Inflammation |
|
| dc.title |
In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats |
|
| dc.type |
Artículo |
|