Effects of Iron Chelators on Pulmonary Iron Overload and Oxidative Stress in β-Thalassemic Mice

Pharmacology
Paranee YatmarkSuthat Fucharoen

Abstract

To evaluate the effect of iron chelators on iron-related pulmonary pathology and oxidative stress in an animal model of β-thalassemia. Pulmonary iron overload was induced in heterozygous β-globin knockout mice (muβth-3/+, BKO). Over a period of 2 weeks, 180 mg of iron/mouse was loaded by intraperitoneal injection of iron dextran, and subsequently treated daily via intraperitoneal with either deferoxamine (DF) or deferiprone (L1) at an equimolar concentration of iron binding (0.2 and 0.6 μmol/g body weight, respectively) for 7 days. Iron loading resulted in iron deposition in peribronchial regions, septa and also in alveolar macrophages with a grading score of 3. This iron burden resulted in lung epithelial injuries, fibrosis and corresponded with increased lipid peroxidation and decreased tissue catalase activity. Treatment with DF or L1 resulted in a reduction of iron-laden alveolar macrophages and decreased oxidative stress and tissue damage, showing the iron mobilizing ability of both compounds. Iron chelation therapy, with DF and L1, may protect against pulmonary damage by sequestering catalytic iron and improving oxidative status. It may be beneficial in the prevention of pulmonary complications in thalassemia.

Citations

Apr 16, 2017·American Journal of Respiratory and Critical Care Medicine·Suzanne M CloonanGregory J Quinlan
Dec 26, 2018·Journal of Toxicology·Arwa A El-SheikhSamaa Salah AbdEl-Fatah
Mar 16, 2017·Redox Report : Communications in Free Radical Research·Amira Abdel Moneam AdlySara Hamed Elmetwally
Jun 28, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Haipeng ChengZiqiang Luo

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