TY - JOUR
T1 - Zn/Ga-DFO iron-chelating complex attenuates the inflammatory process in a mouse model of asthma
AU - Bibi, Haim
AU - Vinokur, Vladimir
AU - Waisman, Dan
AU - Elenberg, Yigal
AU - Landesberg, Amir
AU - Faingersh, Anna
AU - Yadid, Moran
AU - Brod, Vera
AU - Pesin, Jimy
AU - Berenshtein, Eduard
AU - Eliashar, Ron
AU - Chevion, Mordechai
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Asthma
KW - Inflammation
KW - Iron
KW - Iron chelation
KW - OVA-induced asthma model
UR - http://www.scopus.com/inward/record.url?scp=84903219887&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.redox.2014.06.009
DO - https://doi.org/10.1016/j.redox.2014.06.009
M3 - Article
C2 - 25009783
SN - 2213-2317
VL - 2
SP - 814
EP - 819
JO - Redox Biology
JF - Redox Biology
IS - 1
ER -