Pathophysiology of iron overload

Annals of the New York Academy of Sciences

Volumn 850, Issue , 1998, Pages 191-201

  Hershko, Chaim ^a,b   Link, Gabriela ^b   Cabantchik, Ioav ^c  

^a SHAARE ZEDEK MEDICAL CENTER   (Israel)

^b HEBREW UNIVERSITY   (Israel)

^c HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

ASCORBIC ACID; CHELATING AGENT; FREE RADICAL; HYDROXYL RADICAL; IRON; MEMBRANE LIPID; MEMBRANE PROTEIN; TRANSFERRIN;

CARDIOMYOPATHY; CONFERENCE PAPER; ENERGY METABOLISM; ERYTHROPOIESIS; HUMAN; IRON ABSORPTION; IRON BINDING CAPACITY; IRON BLOOD LEVEL; IRON CHELATION; IRON METABOLISM; IRON OVERLOAD; LIPID PEROXIDATION; MITOCHONDRIAL RESPIRATION; NONHUMAN; PATHOPHYSIOLOGY; RESPIRATORY CHAIN; SIDEROSIS; THALASSEMIA;

EID: 0031871914     PISSN: 00778923     EISSN: None     Source Type: Book Series    
DOI: 10.1111/j.1749-6632.1998.tb10475.x     Document Type: Conference Paper

References (58)

1. COOK, J. D., G. MARSAGLIA, J. W. ESCHBACH et al. 1970. Ferrokinetics: A biologic model for plasma iron exchange in man. J. Clin. Invest. 49: 197-205.
2. HERSHKO, C. & E. A. RACRMILEWITZ. 1979. Mechanism of desferrioxamine-induced iron excretion in thalassaemia. Br. J. Haematol. 42: 125-132.
3. HERSHKO, C. 1975. A study of the chelating agent diethylenetriamine pentaacetic acid using selective radioiron probes of reticuloendothelial and parenchymal iron stores. J. Lab. Clin. Med. 85: 913-921.
4. HERSHKO, C. & E.A. RACHMILEWITZ. 1975. Non transferrin plasma iron in patients with transfusional iron overload. In Proteins of Iron Storage and Transport in Biochemistry and Medicine. R. R. Crichton, Ed.: 437-433. Amersham. The Netherlands.
5. HERSHKO, C., G. GRAHAM, G. W. BATES & E. A. RACHMILEWITZ. 1978. Non-specific serum iron in thalassaemia: an abnormal serum iron fraction of potential toxicity. Br. J. Haematol. 40: 255-263.
6. SINGH, S., R. C. HIDER & J. B. PORTER. 1990. A direct method for quantification of non-transferrin bound iron (NTBPI). Anal. Biochem. 186: 320-323.
7. BATEY, R. G., P. LAI CHUNG FONG & S. SHERLOCK. 1978. The nature of serum iron in primary haemochromatosis. Clin. Sci. 55: 24-28.
8. ANUWATANAKULCHAI, M., P. POOTRAKUL, P. THUVASETHAKUL & P. WASI. 1984. Non-transferrin plasma iron in β-thalassaemia/HbE and haemoglobin H diseases. Scand. J. Haematol. 32: 153-158.
9. WANG, W. C., N. AHMED & M. HANNA. 1986. Non-transferrin-bound iron in long-term transfusion in children with congenital anemias. J. Pediatr. 108: 552-557.
10. WAGSTAFF, M., S. W. PETERS, B. M. JONES & A. JACOBS. 1985. Free iron and iron toxicity in iron overload. Br. J. Haematol. 61: 566-567.
11. GUTTERIDGE, J. M. C., D. A. ROWLEY, E. GRIFFITHS & B. HALLIWELL. 1985. Low-molecular-weight iron complexes and oxygen radical reactions in idiopathic haemochromatosis. Clin. Sci. 68: 463-467.
12. AL-REFAIE, E N., D. G. WICKENS, B. WONKE, G. J. KONTOGHIORGHES & A. V. HOFFBRAND. 1992. Serum non-transferrin-bound iron in beta-thalassaemia major patients treated with desferrioxamine and L1. Br. J Haematol. 82: 431-436.
13. PORTER, J. B., R. D. ABEYSLNGHE, L. MARSHALL, R. C. HIDER & S. SINGH. 1996. Kinetics of removal and reappearance of non-transferrin-bound plasma iron with deferoxamine therapy. Blood 88: 705-713.
14. LINK, G., A. PINSON & C. HERSHKO. 1985. Heart cells in culture: a model of myocardial iron overload and chelation. J. Lab. Clin. Med. 106: 147-153.
15. RANDELL, E. W., J. G. PARKES, N. F. OLIVIERI & D. M. TEMPLETON. 1994. Uptake of non-transferrin-bound iron by both reductive and nonreductive processes is modulated by intracellular iron. J. Biol. Chem. 269: 16046-16053.
16. LINK, G., P. ATHIAS, A. GRYNBERG, A. PINSON & C. HERSHKO. 1989. Effect of iron loading on transmembrane potential, contraction and automaticity of rat ventricular muscle cells in culture. J. Lab. Clin. Med. 113: 103-111.
17. MOREB, J., C. HERSHKO & Y. HASIN. 1988. Effects of acute iron loading on contractility and spontaneous beating rate of cultured rat myocardial cells. Basic Res. Cardiol. 83: 360-368.
18. LINK, G., A. PINSON & C. HERSHKO. 1985. Heart cells in culture: a model of myocardial iron overload and chelation. J. Lab. Clin. Med. 106: 147-153.
19. HERSHKO, C., G. LINK & A. PINSON. 1987. Modification of iron uptake and lipid peroxidation by hypoxia, ascorbic acid, and a-tocopherol in iron-loaded rat myocardial cell cultures. J. Lab. Clin. Med. 110: 355-361.
20. LINK, G., A. PINSON, I. KAHANE & C. HERSHKO. 1989. Iron loading modifies the fatty acid composition of cultured rat myocardial cells and liposomal vesicles: Effect of ascorbate and atocopherol on myocardial lipid peroxidation. J. Lab. Clin. Med. 114: 243-249.
21. HERSHKO, C., G. LINK, A. PINSON, H. H. PETER, P. DOBBIN & R. C. HIDER. 1991. Iron mobilization from myocardial cells by 3-hydroxypyridin-4-one chelators: Studies in rat heart cells in culture. Blood 77: 2049-2053.
22. LINK, G., P. ATHIAS, A. GRYNBERG, C. HERSHKO & A. PINSON. 1991. Iron loading modifies β-adrenergic responsiveness of cultured ventricular myocytes. Cardioscience 2: 27-30.
23. HALLIWELL, B. & J. M. C. GUTTERIDGE. 1990. Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol. 186: 1-85.
24. GODDARD, J. G. & G. D. SWEENEY. 1983. Ferric nitriloacetate: a potent stimulant of in vivo lipid peroxidation in mice. Biochem. Pharmacol. 32: 3879-3882.
25. DILLARD, C. J., J. E. DOWNEY & A. L. TAPPEL. 1984. Effect of antioxidants on lipid peroxidation in iron-loaded rats. Lipids 19: 127-133.
26. HOUGLUM, K., M. FILIP, J. L. WITZTUM & M. CHOIKIER. 1990. Malondialdehyde and 4-hydroxynonenal protein adducts in plasma and liver of rats with iron overload. J. Clin. Invest. 86: 1991-1998.
27. SEYMOUR, C. A. & T. J. PETERS. 1978. Organelle pathology in primary and secondary hemochromatosis with special reference to lysosomal changes. Br. J. Haematol. 40: 239-253.
28. WEIR, M. P., J. F. GIBSON & T.J. PETERS. 1984. Haemosiderin and tissue damage. Cell Biochem. Funct. 2: 186-194.
29. LINK, G., A. PINSON & C. HERSHKO. 1993. Iron loading of cultured cardiac myocytes modifies sarcolemmal structure and increases lysosomal fragility. J. Lab. Clin. Med. 121: 127-134.
30. SCOTT, J. A., B. ANKHAW, E. LOCKE, E. HABER & C. HOMNEY. 1985. The role of free radicalmediated processes in oxygen-related damage in cultured murine myocardial cells. Circ. Res. 56: 72-77.
31. LINK, G., A. PINSON & C. HERSHKO. 1994. The ability of orally effective iron chelators dimethyland diethyl-hydroxypyrid-4-one and of deferoxamine to restore sarcolemmal thiolic enzyme activity in iron-loaded heart cells. Blood 83: 2692-2697.
32. BACON, B. R., C. H. PARK, G. M. BRITTENHAM, R. O'NEILL & A. S. TAVILL. 1985. Hepatic mitochondrial oxidative metabolism in rats with chronic dietary iron overload. Hepatology 5: 789-797.
33. BACON, B. R., R. O'NEILL & R. S. BRITTON. 1993. Hepatic mitochondrial energy production in rats with chronic iron overload. Gastroenterology 105: 1134-1140.
34. LINK, G., R. TIROSH, A. PINSON & C. HERSHKO. 1996. Role of iron in the potentiation of anthracycline toxicity: Identification of heart cell mitochondria as the site of iron-anthracycline interaction. J. Lab. Clin. Med. 127: 272-278.
35. HEYS, A. D. & T. L. DORMANDY. 1981. Lipid peroxidation in iron loaded spleens. Clin. Sci. 60: 295-301.
36. O'CONNELL, M. J., R. J. WARD, H. BAUM & T. J. PETERS. 1985. The role of iron in ferritin- and haemosiderin-mediated lipid peroxidation in liposomes. Biochem. J. 229: 135-139.
37. NIENHUIS, A. W. 1981. Vitamin C and iron. N. Engl. J. Med. 304: 170-171.
38. JACOBS, A. 1977. Low molecular weight intracellular iron transport compartments. Blood 50: 433-436.
39. CRICHTON, R. R. & R. J. WARD. 1992. In Iron and Human Diseases, R. B. Laufer, Ed.: 23-76. CRC Press. Boca Raton, FL.
40. BREUER, W., S. EPSZTEIN & Z. I. CABANTCHIK. 1995. Iron acquired from transferrin by K562 cells is delivered into a cytoplasmic pool of chelatable iron(II). J Biol. Chem. 270: 24209-24215.
41. HERSHKO, C. & D. J. WEATHERALL. 1988. Iron dictating therapy. Crit. Rev. Clin. Lab. Sci. 26: 303-345.
42. ROTHMAN, R. J., A. SERRONI & J. L. FARBER. 1992. Cellular pool of transient ferric iron, chelatable by deferoxamine and distinct from ferritin, that is involved in oxidative cell injury. Molec. Pharmacol. 42: 703-710.
43. PONKA, P., R. W. GRADY, A. WILCZYNSKA & H. M. SCHULMAN. 1984. The effect of various chelating agents on the mobilization of iron from reticulocytes in the presence and absence of pyridoxal isonicotinoyl hydrazone. Biochim. Biophys. Acta 802: 477-489.
44. BAKER, E., D. RICHARDSON, S. GROSS & P. PONKA P. 1992. Evaluation of the iron chelation potential of hydrazones of pyridoxal, salicylaldehyde and 2-hydroxy-1-naphthylaldehyde using the hepatocyte in culture. Hepatology 15: 492-501.
45. KLAUSNER, R. D., T. A. ROUAULT & J. B. HARFORD. 1993. Regulating the fate of mRNA: The control of cellular iron metabolism. Cell 72: 19-28.
46. St. PIERRE, T. G., D. R. RICHARDSON, E. BAKER & J. WEBB. 1992. A low-spin iron complex in human melanoma and rat hepatoma cells and a high-spin iron(II) complex in rat hepatoma cells. Biochim. Biophys. Acta 1135: 154-158.
47. POLLACK, S. 1992. Receptor mediated iron uptake and intracellular iron transport. Am. J Hematol. 39: 113-117.
48. BREUER, W., S. EPSZTEJN, P. MILLGRAM & Z. I. CABANTCHIK. 1995. Transport of iron and other transition metals into cells as revealed by a fluorescent probe. Am. J. Physiol. 268: C1354-1361.
49. BREUER, W., S. EPSZTEIN & Z. I. CABANTCHIK. 1997. Dynamics of the cytosolic chelatable iron pool of K562 cells. FEBS Lett. 382: 304-308.
50. HERSHKO, C. 1977. Storage iron regulation. Progr. Hematol. 10: 105-148.
51. HERSHKO, C. 1978. Determinants of fecal and urinary iron excretion in desferrioxamine treated rats. Blood 51: 415-424.
52. HERSHKO, C., R. W. GRADY & A. CERAMI. 1978. Mechanism of iron chelation in the hypertransfused rat: definition of the two alternative pathways of iron mobilization. J. Lab. Clin. Med. 92, 144-151.
53. HERSHKO, C, G. RIVKIN, G. LINK, E. SIMHON, R. L. CYJON & J. Y. KLEIN. 1996. IRC11, a new synthetic chelator with selective interaction with catabolic red cell iron. Blood 88 (Suppl. 1): abstract 1951.
54. GABUTTI, V. & C. BORGNA-PIGNATTI. 1994. Clinical manifestations and therapy of transfusional haemosiderosis. Clin. Haematol. 7: 919-940.
55. PORTER, J. B., E. R. HUEHNS & R. C. HIDER. 1989. The development of iron chelating drugs. Clin. Haematol. 2: 257-292.
56. PORTER, J. B., K. P. HOYES, R. D. ABEYSINGHE, P. N. BROOKS, E. R. HUEHNS & R. C. HIDER. 1991. Comparison of subacute toxicity and efficacy of orally active 3-hydroxypyridin-4-one iron chelators. Blood 78: 2727-2734.
57. HERSHKO, C., R. W. GRADY & G. LINK. 1984. Phenolic ethylenediamine derivatives: A study of orally effective iron chelators. J. Lab. Clin. Med. 103: 337-346.
58. SCHNEBLI, H. P., P. ACKLIN, P. BUHLMAYER et al. 1997. Progress towards new, orally active iron chelators. Presented at Sixth International Conference on Thalassaemia and the Haemoglobinopathies. St. Pauls's Bay, Malta. April 5-10, 1997. Abstract # 216.