Abstract
The efficacy of Bleomycin (BLM) as an antineoplastic drug is limited to the development of dose and time-dependent pulmonary fibrosis. This study was intended to investigate the effect of N-acetylcysteine (NAC) on BLM-induced pulmonary fibrosis on rats.Twenty rats were randomly divided tothe following four groups: Group one served as control; group two receivedBLM (15 mg/kg, intraperitoneal (i.p.)) for 5 consecutive days; group three received NAC (200 mg/kg, i.p.) for 5 consecutive days; and group four received NACone hour before BLMfor 5 days. The expression of connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), silent information regulator l (SIRT1), AMP-activated protein kinase (AMPK)were determined by qRT-PCR in lung tissues. The changes in transforming growth factor-beta1 (TGF-β1), tumor necrosis factor-α (TNF-α), interleukin-β1(IL-β1) and nuclear factor kappa-β (NF-Kβ) in serum were measured by ELISA. The tissue antioxidant status was determined biochemically. BLM administration caused pulmonary fibrosis as evidenced by increased levels of inflammatory mediators (TGF-β1, TNF-α, IL-β1 and NF-Kβ)in serum (P<0.05), elevated lipid peroxidation and nitric oxide and depleted endogenous antioxidants in lung tissue(P<0.05). The expression levels of SIRT1 and AMPK were significantly decreased(P<0.05), while the expression levels of CTGF and PDGF were increased significantly in the BLM group as compared to the control group(P<0.05). These alterations werenormalizedby NAC intervention. NAC markedly attenuated the lung histopathological changes and reduced collagen deposition.These results suggested that NAC exerted anameliorative effect against BLM-induced oxidative damage and pulmonary fibrosisvia SIRT1/ AMPK/ NF-Kβ pathways.
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