Modulation of bleomycin-induced oxidative stress and pulmonary fibrosis by N-acetylcysteine in rats via AMPK/SIRT1/NF-κβ.

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 in rats. Twenty rats were randomly divided to the following four groups: Group one served as control; group two received BLM (15 mg/kg, intraperitoneal (ip)) for five consecutive days; group three received NAC (200 mg/kg, ip) for five consecutive days; and group four received NAC 1 hour before BLM for 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), tumour necrosis factor-α (TNF-α), interleukin-β1 (IL-β1) and nuclear factor kappa-β (NF-κβ) 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-κβ) in serum (P < .05), elevated lipid peroxidation and nitric oxide and depleted endogenous antioxidants in lung tissue (P < .05). The expression levels of SIRT1 and AMPK were significantly decreased (P < .05), while the expression levels of CTGF and PDGF were increased significantly in the BLM group as compared to the control group (P < .05). These alterations were normalized by NAC intervention. NAC markedly attenuated the lung histopathological changes and reduced collagen deposition. These results suggest that NAC exerted an ameliorative effect against BLM-induced oxidative damage and pulmonary fibrosis via SIRT1/ AMPK/ NF-κβ pathways.