Zn/Ga−DFO iron–chelating complex attenuates the inflammatory process in a mouse model of asthma
| Autor: | Mordechai Chevion, Vera Brod, Dan Waisman, Haim Bibi, Eduard Berenshtein, Ron Eliashar, Jimy Pesin, Yigal Elenberg, Anna Faingersh, Moran Yadid, Amir Landesberg, Vladimir Vinokur |
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| Rok vydání: | 2014 |
| Předmět: |
Iron Chelating
Neutrophils Clinical Biochemistry Gallium Pharmacology Biochemistry Anti-asthmatic Agent Mice Anti-Asthmatic Agents Lung lcsh:QH301-705.5 Mice Inbred BALB C lcsh:R5-920 biology Chemistry Iron Chelating Agents respiratory system OVA-induced asthma model Deferoxamine Iron chelation Female medicine.symptom lcsh:Medicine (General) Bronchoalveolar Lavage Fluid Injections Intraperitoneal Research Paper medicine.drug inorganic chemicals Ovalbumin Iron Radical Inflammation Organometallic Compounds medicine Animals Administration Intranasal Asthma Organic Chemistry medicine.disease Eosinophils Disease Models Animal lcsh:Biology (General) Ferritins Immunology biology.protein |
| Zdroj: | Redox Biology, Vol 2, Iss C, Pp 814-819 (2014) Redox Biology |
| ISSN: | 2213-2317 |
| DOI: | 10.1016/j.redox.2014.06.009 |
| Popis: | Background Redox-active iron, a catalyst in the production of hydroxyl radicals via the Fenton reaction, is one of the key participants in ROS-induced tissue injury and general inflammation. According to our recent findings, an excess of tissue iron is involved in several airway-related pathologies such as nasal polyposis and asthma. Objective To examine the anti-inflammatory properties of a newly developed specific iron–chelating complex, Zn/Ga−DFO, in a mouse model of asthma. Materials and methods Asthma was induced in BALBc mice by ovalbumin, using aluminum hydroxide as an adjuvant. Mice were divided into four groups: (i) control, (ii) asthmatic and sham-treated, (iii) asthmatic treated with Zn/Ga−DFO [intra-peritoneally (i/p) and intra-nasally (i/n)], and (iv) asthmatic treated with Zn/Ga−DFO, i/n only. Lung histology and cytology were examined. Biochemical analysis of pulmonary levels of ferritin and iron-saturated ferritin was conducted. Results The amount of neutrophils and eosinophils in bronchoalveolar lavage fluid, goblet cell hyperplasia, mucus secretion, and peri-bronchial edema, showed markedly better values in both asthmatic-treated groups compared to the asthmatic non-treated group. The non-treated asthmatic group showed elevated ferritin levels, while in the two treated groups it returned to baseline levels. Interestingly, i/n-treatment demonstrated a more profound effect alone than in a combination with i/p injections. Conclusion In this mouse model of allergic asthma, Zn/Ga−DFO attenuated allergic airway inflammation. The beneficial effects of treatment were in accord with iron overload abatement in asthmatic lungs by Zn/Ga−DFO. The findings in both cellular and tissue levels supported the existence of a significant anti-inflammatory effect of Zn/Ga−DFO. Graphical abstract Highlights Asthma pathophysiology was shown to be associated with iron overload. A therapeutic effect of the novel iron–chelating complexes was demonstrated. Histological and cytological markers of inflammation were studied. The complexes could be administered intranasally or by intraperitonneal injections. |
| Databáze: | OpenAIRE |
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