title: Effect of iron chelators on labile iron and oxidative status of thalassaemic erythroid cells.
abstract: OBJECTIVE
  Iron accumulation in vital organs such as heart and liver is a major pathology in beta-thalassaemia. It may also affect mature RBCs and developing erythroid precursors. The cellular damage is mainly caused by the labile iron pool (LIP) and is mediated by reactive oxygen species (ROS). We have previously shown that thalassaemic RBCs and their precursors have more LIP and ROS than their normal counterparts. We now report the effect of clinically relevant iron chelators on these parameters.
  
  
  METHODS
  RBCs, reticulocytes and cultured erythroid precursors derived from patients with beta-thalassaemia were studied for LIP and oxidative stress parameters by flow-cytometry.
  
  
  RESULTS
  In vitro treatment with deferiprone, deferasirox and deferoxamine reduced the cytosolic LIP in RBCs and reticulocytes, and both the cytosolic and mitochondrial LIP in cultured erythroid precursors. This was associated with reduced oxidative stress (ROS and external phosphatidylserine). While the effect of deferiprone and deferasirox was fast (within 10 min), deferoxamine affected these parameters after 24 h, suggesting a slower rate of entry.
  
  
  CONCLUSIONS
  The chelators studied reduce the LIP and the oxidative status of thalassaemic RBC and their precursors. Whether these effects directly improve ineffective erythropoiesis and RBC survival remains to be shown.
authors.affiliation: Department of Haematology, Hadassah Hebrew University Medical Centre, Jerusalem, Israel.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Prus
authors.forename: Eitan
authors.initials: E
authors.lastname: Fibach
mesh_terms: D001565:Benzoates / Q000494:pharmacology; D000077588:Deferasirox; D000077543:Deferiprone; D003676:Deferoxamine / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D041905:Erythroid Cells / Q000187:drug effects* / Q000378:metabolism*; D005293:Ferritins / Q000097:blood; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000097:blood*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D019190:Iron Overload / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D018384:Oxidative Stress / Q000187:drug effects*; D010718:Phosphatidylserines / Q000097:blood; D011728:Pyridones / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000097:blood; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology; D017086:beta-Thalassemia / Q000097:blood* / Q000150:complications / Q000188:drug therapy*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D010718:Phosphatidylserines; D011728:Pyridones; D017382:Reactive Oxygen Species; D014230:Triazoles; D000077543:Deferiprone; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox