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Protective Effect of Infliximab, a Tumor Necrosis Factor-Alfa Inhibitor, on Bleomycin-Induced Lung Fibrosis in Rats

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Abstract

We aimed to investigate the preventive effect of Infliximab (IFX), a tumor necrosis factor (TNF)-α inhibitor, on bleomycin (BLC)-induced lung fibrosis in rats. Rats were assigned into four groups as follows: I—BLC group, a single intra-tracheal BLC (2.5 mg/kg) was installed; II—control group, a single intra-tracheal saline was installed; III—IFX + BLC group, a single-dose IFX (7 mg/kg) was administered intraperitoneally (i.p.), 72 h before the intra-tracheal BLC installation; IV—IFX group, IFX (7 mg/kg) was administered alone i.p. on the same day with IFX + BLC group. All animals were sacrificed on the 14th day of BLC installation. Levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, interleukin (IL)-6, periostin, YKL-40, nitric oxide (NO) in rat serum were measured, as well as, myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity, and reduced glutathione (GSH), hydroxyproline, malondialdehyde (MDA) content in lung homogenates. Lung tissues were stained with hematoxylin and eosin (H&E) for quantitative histological evaluation. The inducible nitric oxide synthase (iNOS) expression and cell apoptosis in the lung tissues were determined quantitatively by immunohistochemical staining (INOS) and by TUNNEL staining, respectively. BLC installation worsened antioxidant status (such as SOD, CAT, GPx, GSH, MPO), while it increased the serum TNF-α, TGF-β, IL-6, periostin, YKL-40, and lipid peroxidation, and collagen deposition, measured by MDA and hydroxyproline, respectively. IFX pretreatment improved antioxidant status as well as BLC-induced lung pathological changes, while it decreased the TNF-α, TGF-β, IL-6, periostin, YKL-40, lipid peroxidation and collagen deposition. Finally, histological, immunohistochemical, and TUNNEL evidence also supported the ability of IFX to prevent BLC-induced lung fibrosis. The results of the present study indicate that IFX pretreatment can attenuate BLC-induced pulmonary fibrosis.

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Conflict of Interest

The authors have no conflict of interest to declare. Funding for this study was received from “Namik Kemal University, Scientific Research Projects Unit”, Project No: NKUBAP.00.20.AR.1417

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Authors and Affiliations

  1. Department of Pulmonary, Critical Care and Sleep Medicine, Namik Kemal University, Tekirdag, Turkey

    Nejat Altintas

  2. Department of Histology and Embryology, University of Namik Kemal, Tekirdag, Turkey

    Mustafa Erboga & Cevat Aktas

  3. Department of Internal Medicine, University of Namik Kemal, Tekirdag, Turkey

    Bulent Bilir

  4. Department of Biochemistry, University of Namik Kemal, Tekirdag, Turkey

    Murat Aydin, Zehra Ates & Ahmet Gurel

  5. Department of Pulmonology, Derince Training Hospital, Derince, Kocaeli, Turkey

    Aysun Sengul

  6. Department of Biostatistics, University of Namik Kemal, Tekirdag, Turkey

    Birol Topcu

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  1. Nejat Altintas
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Altintas, N., Erboga, M., Aktas, C. et al. Protective Effect of Infliximab, a Tumor Necrosis Factor-Alfa Inhibitor, on Bleomycin-Induced Lung Fibrosis in Rats. Inflammation 39, 65–78 (2016). https://doi.org/10.1007/s10753-015-0224-z

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