title: Zn/Ga-DFO iron-chelating complex attenuates the inflammatory process in a mouse model of asthma.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pediatric Department, Barzilai Medical Center, Ben Gurion University School of Medicine, Ashkelon, Be'er Sheva, Israel.
authors.forename: Haim
authors.initials: H
authors.lastname: Bibi
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, The Hebrew University, Jerusalem, Israel.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vinokur
authors.affiliation: Department of Neonatology, Carmel Medical Center, Haifa, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Waisman
authors.affiliation: Pediatric Department, Barzilai Medical Center, Ben Gurion University School of Medicine, Ashkelon, Be'er Sheva, Israel.
authors.forename: Yigal
authors.initials: Y
authors.lastname: Elenberg
authors.affiliation: Faculty of Biomedical Engineering, Technion, Haifa, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Landesberg
authors.affiliation: Faculty of Biomedical Engineering, Technion, Haifa, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Faingersh
authors.affiliation: Faculty of Biomedical Engineering, Technion, Haifa, Israel.
authors.forename: Moran
authors.initials: M
authors.lastname: Yadid
authors.affiliation: Ischemia-Shock Research Laboratory, Department of Medicine, Carmel Medical Center, Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Vera
authors.initials: V
authors.lastname: Brod
authors.affiliation: Faculty of Biomedical Engineering, Technion, Haifa, Israel.
authors.forename: Jimy
authors.initials: J
authors.lastname: Pesin
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, The Hebrew University, Jerusalem, Israel.
authors.forename: Eduard
authors.initials: E
authors.lastname: Berenshtein
authors.affiliation: Department of Otolaryngology/Head & Neck Surgery, Hebrew University School of Medicine, - Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Eliashar
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, The Hebrew University, Jerusalem, Israel.
authors.forename: Mordechai
authors.initials: M
authors.lastname: Chevion
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001249:Asthma / Q000473:pathology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003676:Deferoxamine / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology; D005260:Female; D005293:Ferritins / Q000378:metabolism; D005708:Gallium / Q000737:chemistry; D007274:Injections, Intraperitoneal; D007502:Iron Chelating Agents / Q000737:chemistry / Q000627:therapeutic use*; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology; D009942:Organometallic Compounds / Q000737:chemistry / Q000627:therapeutic use*; D010047:Ovalbumin / Q000633:toxicity
chemical_list: D018927:Anti-Asthmatic Agents; D007502:Iron Chelating Agents; D009942:Organometallic Compounds; C086228:zinc-desferrioxamine; D010047:Ovalbumin; D005293:Ferritins; D005708:Gallium; D003676:Deferoxamine
keywords: Asthma; Inflammation; Iron; Iron chelation; OVA-induced asthma model