title: Tiron ameliorates oxidative stress and inflammation in a murine model of airway remodeling.
abstract: Airway remodeling includes lung structural changes that have a role in the irreversibility of pulmonary dysfunction shown in chronic bronchial asthmatics. The current experiment investigated the effect of the mitochondrial antioxidant, tiron in comparison with dexamethasone (DEXA) on airway remodeling in chronic asthma. Sensitized BALB/c mice were challenged with ovalbumin (OVA) aerosol for 8weeks, OVA sensitized-challenged mice were treated with either DEXA or tiron, respectively. After that, lung tissue and bronchoaveolar lavage fluid (BALF) were used for measurement of different biological markers. Lungs were examined for histopathological changes and immunohistochemistry. Upon comparing with vehicle treated animals, trion or DEXA treatment significantly reduced eosinophils, lymphocytes, neutrophils and macrophages count in the BALF. Both drugs significantly alleviated chronic OVA-induced oxidative stress as illustrated by decreased pulmonary malondialdenhyde (MDA) and increased glutathione (GSH) and superoxide dismutase (SOD) levels. Asthmatic mice exhibited elevated levels of NOx, IL-13 and TGF-β1 that were reduced by DEXA and tiron. Histopathological changes and increased immunoreactivity of nuclear factor-Kappa B (NF-κ B) in OVA-challenged mice were minimized by tiron and DEXA treatment. In conclusion, in this model of chronic asthma DEXA and tiron ameliorated airway remodeling and inflammation in experimental chronic asthma with no difference between the effect of tiron and DEXA. Tiron has a potential role as adjuvant treatment in chronic asthma.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medicine, Suez canal University, Egypt. Electronic address: n_elsherbeeny@hotmail.com.
authors.forename: Nagla A
authors.initials: NA
authors.lastname: El-Sherbeeny
authors.affiliation: Department of Histology and Cell Biology, Faculty of Medicine, Zagazig University, Egypt.
authors.forename: Zeinab A
authors.initials: ZA
authors.lastname: Hassan
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medicine, Cairo University, Egypt.
authors.forename: Hayam
authors.initials: H
authors.lastname: Ateyya
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000627:therapeutic use*; D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D003907:Dexamethasone / Q000627:therapeutic use; D004804:Eosinophils / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000188:drug therapy*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D003907:Dexamethasone; D013482:Superoxide Dismutase
keywords: Airway remodeling; Antioxidants; Dexamethasone; TGF-β1; Tiron