title: Protective Effect of Infliximab, a Tumor Necrosis Factor-Alfa Inhibitor, on Bleomycin-Induced Lung Fibrosis in Rats.
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.
authors.affiliation: Department of Pulmonary, Critical Care and Sleep Medicine, Namik Kemal University, Tekirdag, Turkey. nejataltintas@gmail.com.
authors.forename: Nejat
authors.initials: N
authors.lastname: Altintas
authors.affiliation: Department of Histology and Embryology, University of Namik Kemal, Tekirdag, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Erboga
authors.affiliation: Department of Histology and Embryology, University of Namik Kemal, Tekirdag, Turkey.
authors.forename: Cevat
authors.initials: C
authors.lastname: Aktas
authors.affiliation: Department of Internal Medicine, University of Namik Kemal, Tekirdag, Turkey.
authors.forename: Bulent
authors.initials: B
authors.lastname: Bilir
authors.affiliation: Department of Biochemistry, University of Namik Kemal, Tekirdag, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Aydin
authors.affiliation: Department of Pulmonology, Derince Training Hospital, Derince, Kocaeli, Turkey.
authors.forename: Aysun
authors.initials: A
authors.lastname: Sengul
authors.affiliation: Department of Biochemistry, University of Namik Kemal, Tekirdag, Turkey.
authors.forename: Zehra
authors.initials: Z
authors.lastname: Ates
authors.affiliation: Department of Biostatistics, University of Namik Kemal, Tekirdag, Turkey.
authors.forename: Birol
authors.initials: B
authors.lastname: Topcu
authors.affiliation: Department of Biochemistry, University of Namik Kemal, Tekirdag, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Gurel
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D000069285:Infliximab / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000097:blood
chemical_list: D000975:Antioxidants; D015815:Cell Adhesion Molecules; D015850:Interleukin-6; C512836:Postn protein, rat; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; D009569:Nitric Oxide; D008315:Malondialdehyde; D000069285:Infliximab; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: idiopathic pulmonary fibrosis; inflammation; infliximab; lung fibrosis; transforming growth factor-beta; tumor necrosis factor-alpha; tumor necrosis factor-alpha inhibitors