title: Effects of Iron Chelators on Pulmonary Iron Overload and Oxidative Stress in β-Thalassemic Mice.
abstract: OBJECTIVE
  To evaluate the effect of iron chelators on iron-related pulmonary pathology and oxidative stress in an animal model of β-thalassemia.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors: Paranee
authors: P
authors: Yatmark
authors: Noppawan Phumala
authors: NP
authors: Morales
authors: Urai
authors: U
authors: Chaisri
authors: Surasak
authors: S
authors: Wichaiyo
authors: Warinkarn
authors: W
authors: Hemstapat
authors: Somdet
authors: S
authors: Srichairatanakool
authors: Saovaros
authors: S
authors: Svasti
authors: Suthat
authors: S
authors: Fucharoen
mesh_terms: D000818:Animals; D000931:Antidotes / Q000627:therapeutic use; D000077543:Deferiprone; D003676:Deferoxamine / Q000627:therapeutic use; D003911:Dextrans / Q000627:therapeutic use; D005260:Female; D005355:Fibrosis / Q000473:pathology; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects*; D011728:Pyridones / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000473:pathology; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000931:Antidotes; D003911:Dextrans; D007502:Iron Chelating Agents; D011728:Pyridones; D055544:beta-Globins; D000077543:Deferiprone; D003676:Deferoxamine