期刊
LIFE SCIENCES
卷 82, 期 23-24, 页码 1142-1153出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2008.03.018
关键词
pulmonary fibrosis; bleomycin; DAS; NF-kappa B; iNOS; TNF-alpha; IL-1 beta
Diallylsulfide (DAS), an antioxidant and anti-inflammatory agent was evaluated for its ability to repress lung fibrosis induced by bleomycin in Wistar rats. A single intra tracheal administration of bleomycin (6.5 U/kg BW) was administered to pulmonary fibrosis group, while DAS (120 mg/kg BW) was administered intraperitoneally throughout the experimental period. Fibrotic changes in the lungs were estimated by measuring lung hydroxyproline content. Bleomycin administration significantly (P < 0.05) reduced the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the lung tissues. Bleomycin caused a significant decrease in the level of reduced glutathione (GSH), which was accompanied with significant increase in lipid peroxidation (LPO) level, and myeloperoxidase (MPO) activity, in the lung tissues. An increase in the level of cell counts in bronchoalveolar lavage fluid (BALF) was observed in bleomycin induced group. DAS administration altered the levels of enzymic antioxidants, TBARS, MPO and GSH towards normal values. Histopathological analysis and picrosirius red staining showed an increased collagen deposition in rats receiving bleomycin alone that was decreased upon DAS treatment. Immunohistochemical studies revealed that DAS reduced the bleomycin-induced activation of inducible nitric oxide synthase (iNOS) and nuclear factor kappa-B (NF-kappa B) and decreased the augmented levels of the early inflammatory cytokines, turnout necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), in the lung tissues. The present study provides evidence that DAS might serve as a novel target for the therapeutic treatment of lung fibrosis. (c) 2008 Elsevier Inc. All rights reserved.
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