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http://dspace.mediu.edu.my:8181/xmlui/handle/10261/2971| Title: | In vivo antioxidant treatment protects against bleomycin-induced lung damage in rats |
| Keywords: | Pulmonary fibrosis Bleomycin Rat N-acetylcysteine Inflammation |
| Publisher: | Wiley-Blackwell |
| 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. 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 reviewed |
| URI: | http://dspace.mediu.edu.my:8181/xmlui/handle/10261/2971 |
| Other Identifiers: | British Journal of Pharmacology 138(6): 1037–1048 (2003) 0007-1188 http://hdl.handle.net/10261/2971 10.1038/sj.bjp.0705138 |
| Appears in Collections: | Digital Csic |
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