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Original Paper

Effect of Iron Chelators on Labile Iron and Oxidative Status of Thalassaemic Erythroid Cells

Prus E. · Fibach E.

Author affiliations

Department of Haematology, Hadassah Hebrew University Medical Centre, Jerusalem, Israel

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Acta Haematol 2010;123:14–20

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: June 09, 2009
Accepted: September 23, 2009
Published online: November 18, 2009
Issue release date: December 2009

Number of Print Pages: 7
Number of Figures: 3
Number of Tables: 0

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: https://www.karger.com/AHA

Abstract

Background/Aims: Iron accumulation in vital organs such as heart and liver is a major pathology in β-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 β-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. Conclusion: 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.

© 2009 S. Karger AG, Basel


References

  1. Kwiatkowski JL, Cohen AR: Iron chelation therapy in sickle-cell disease and other transfusion-dependent anemias. Hematol Oncol Clin North Am 2004;18:1355–1377, ix.
  2. Taher A: Iron overload in thalassemia and sickle cell disease. Semin Hematology 2005;42:5–9.
  3. Rund D, Rachmilewitz E: Beta-thalassemia. N Engl J Med 2005;353:1135–1146.
  4. Beutler E: Iron storage disease: facts, fiction and progress. Blood Cells, Mol Dis 2007;39:140–147.
  5. Greenberg PL: Myelodysplastic syndromes: iron overload consequences and current chelating therapies. J Natl Compr Canc Netw 2006;4:91–96.
  6. Wickramasinghe SN: Congenital dyserythropoietic anaemias: clinical features, haematological morphology and new biochemical data. Blood Rev 1998;12:178–200.
  7. Weatherall DJ: Pathophysiology of thalassaemia. Baillière’s Clin Haematol 1998;11:127–146.
  8. Cappellini MD, Piga A: Current status in iron chelation in hemoglobinopathies. Curr Mol Med 2008;8:663–674.
  9. Kohen R, Nyska A: Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicol Pathol 2002;30:620–650.
  10. Amer J, Fibach E: Oxidative status of platelets in normal and thalassemic blood. Thromb Haemost 2004;92:1052–1059.
  11. Jacobs A: Low molecular weight intracellular iron transport compounds. Blood 1977;50:433–439.
  12. Prus E, Fibach E: The labile iron pool in human erythroid cells. Br J Haematol 2008;142:301–307.
  13. Amer J, Atlas D, Fibach E: N-acetylcysteine amide (AD4) attenuates oxidative stress in beta-thalassemia blood cells. Biochim Biophys Acta 2008;1780:249–255.
  14. Fibach E, Manor D, Oppenheim A, Rachmilewitz EA: Proliferation and maturation of human erythroid progenitors in liquid culture. Blood 1989;73:100–103.
  15. Fibach E, Prus E: Differentiation of human erythroid cells in culture; in Coligan J, Bierer B, Margulies D, Shevach E, Strober W (eds): Current Protocols in Immunology. Edison, John Wiley & Sons, 2005, vol 2 (suppl 69), pp 22.F27.21–10.
  16. Prus E, Fibach E: Flow cytometry measurement of the labile iron pool in human hematopoietic cells. Cytometry A 2007;73:22–27.
  17. Leimberg JM, Prus E, Link G, Fibach E, Konijn AM: Iron-chelator complexes as iron sources for early developing human erythroid precursors. Transl Res 2008;151:88–96.
  18. Weston SA, Parish CR: New fluorescent dyes for lymphocyte migration studies. Analysis by flow cytometry and fluorescence microscopy. J Immunol Methods 1990;133:87–97.
  19. Weston SA, Parish CR: Calcein: a novel marker for lymphocytes which enter lymph nodes. Cytometry 1992;13:739–749.
  20. Breuer W, Epsztejn S, Cabantchik ZI: Iron acquired from transferrin by K562 cells is delivered into a cytoplasmic pool of chelatable iron(II). J Biol Chem 1995;270:24209–24215.
  21. Petrat F, Weisheit D, Lensen M, de Groot H, Sustmann R, Rauen U: Selective determination of mitochondrial chelatable iron in viable cells with a new fluorescent sensor. Biochem J 2002;362:137–147.
  22. Baker E, Richardson D, Gross S, Ponka P: Evaluation of the iron chelation potential of hydrazones of pyridoxal, salicylaldehyde and 2-hydroxy-1-naphthylaldehyde using the hepatocyte in culture. Hepatology 1992;15:492–501.
  23. Crowe WE, Maglova LM, Ponka P, Russell JM: Human cytomegalovirus-induced host cell enlargement is iron dependent. Am J Physiol Cell Physiol 2004;287:1023–1030.
    External Resources
  24. Epsztejn S, Kakhlon O, Glickstein H, Breuer W, Cabantchik I: Fluorescence analysis of the labile iron pool of mammalian cells. Anal Biochem 1997;248:31–40.
  25. Amer J, Goldfarb A, Fibach E: Flow cytometric measurement of reactive oxygen species production by normal and thalassaemic red blood cells. Eur J Haematol 2003;70:84–90.
  26. Bass DA, Parce JW, Dechatelet LR, Szejda P, Seeds MC, Thomas M: Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J Immunol 1983;130:1910–1917.
  27. Koopman G, Reutelingsperger CP, Kuijten GA, Keehnen RM, Pals ST, van Oers MH: Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood 1994;84:1415–1420.
  28. Konijn AM, Tal R, Levy R, Matzner Y: Isolation and fractionation of ferritin from human term placenta: a source for human isoferritins. Anal Biochem 1985;144:423–428.
  29. Loken MR, Shah VO, Dattilio KL, Civin CI: Flow cytometric analysis of human bone marrow. I. Normal erythroid development. Blood 1987;69:255–263.
  30. Loken MR, Civin CI, Bigbee WL, Langlois RG, Jensen RH: Coordinate glycosylation and cell surface expression of glycophorin A during normal human erythropoiesis. Blood 1987;70:1959–1961.
  31. Konijn AM, Glickstein H, Vaisman B, Meyron-Holtz EG, Slotki IN, Cabantchik ZI: The cellular labile iron pool and intracellular ferritin in K562 cells. Blood 1999;94:2128–2134.
  32. Shalev O, Repka T, Goldfarb A, Grinberg L, Abrahamov A, Olivieri NF, Rachmilewitz EA, Hebbel RP: Deferiprone (L1) chelates pathologic iron deposits from membranes of intact thalassemic and sickle red blood cells both in vitro and in vivo. Blood 1995;86:2008–2013.
  33. Shalev O, Hileti D, Nortey P, Hebbel RP, Hoffbrand VA: Transport of 14C-deferiprone in normal, thalassaemic and sickle red blood cells. Br J Haematol 1999;105:1081–1083.
  34. Fibach E, Rachmilewitz EA: The two-step liquid culture: a novel procedure for studying maturation of human normal and pathological erythroid precursors. Stem Cells 1993;11(suppl 1):36–41.
  35. Zhang AS, Sheftel AD, Ponka P: Intracellular kinetics of iron in reticulocytes: evidence for endosome involvement in iron targeting to mitochondria. Blood 2005;105:368–375.
  36. Leimberg J, Prus E, Link G, Fibach E, Konijn A: Iron-chelator complexes as iron sources for early developing human erythroid precursors. Transl Res 2008;151:88–96.
  37. Kalantar-Zadeh K, Rodriguez RA, Humphreys MH: Association between serum ferritin and measures of inflammation, nutrition and iron in haemodialysis patients. Nephrol Dial Transplant 2004;19:141–149.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: June 09, 2009
Accepted: September 23, 2009
Published online: November 18, 2009
Issue release date: December 2009

Number of Print Pages: 7
Number of Figures: 3
Number of Tables: 0

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: https://www.karger.com/AHA


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