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Modulation of bleomycin‐induced oxidative stress and pulmonary fibrosis by N‐acetylcysteine in rats via AMPK/SIRT1/NF‐κβ
Author(s) -
Mansour Heba H.,
Omran Mervat M.,
Hasan Hesham F.,
El kiki Shereen M.
Publication year - 2020
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13378
Subject(s) - ctgf , bleomycin , pulmonary fibrosis , fibrosis , medicine , endocrinology , oxidative stress , ampk , growth factor , tumor necrosis factor alpha , connective tissue , pharmacology , chemistry , protein kinase a , pathology , kinase , receptor , biochemistry , chemotherapy
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.