Prospects for introducing deferiprone as potent pharmaceutical antioxidant

Frontiers in Bioscience - Elite

Volumn 1 E, Issue 1, 2009, Pages 161-178

  Kontoghiorghes, George J ^a  

^a Postgraduate Research Institute of Science Technology Environment and Medicine Limassol   (Cyprus)

Author keywords

Antioxidant therapy; Antioxidants; Chelators; Copper; Deferasirox; Deferiprone; Deferoxamine; Free radical toxicity; Iron; Metal ions; Review; Targeting

Indexed keywords

ANTIOXIDANT; COPPER; DEFERIPRONE; FREE RADICAL; IRON; IRON CHELATING AGENT; PYRIDONE DERIVATIVE;

CHELATION THERAPY; DRUG DEVELOPMENT; HUMAN; METABOLIC DISORDER; METABOLISM; METHODOLOGY; REVIEW;

ANTIOXIDANTS; CHELATION THERAPY; COPPER; DRUG DISCOVERY; FREE RADICALS; HUMANS; IRON; IRON CHELATING AGENTS; METABOLIC DISEASES; PYRIDONES;

EID: 70350685257     PISSN: 19450494     EISSN: 19450508     Source Type: Journal    
DOI: None     Document Type: Article

References (96)

1. Denisov, E. T., & I. B. Afanas'ev: Oxidation and antioxidants in organic chemistry and biology. CRC Press, Taylor and Francis group. Boca Raton. (2005)
2. Halliwell, B., J. M. C. Gutteridge, & C. E. Cross: Free radicals, antioxidants and human disease: Where are we now? J Lab Clin Med 119, 598-620 (1992)
3. Kontoghiorghes, G. J.: Iron chelation in biochemistry and medicine. Ed: Rice-Evans C., Rechelieu Press, London. "Free radicals, oxidant stress and drug action". 277-303 (1987)
4. Afanas'ev, I. B.: Superoxide and nitric oxide in pathological conditions associated with iron overload. The effects of antioxidants and chelators. Curr Med Chem 12, 2731-2739 (2005) (Pubitemid 41601570)
5. Kontoghiorghes, G. J., K. Neocleous, & A. Kolnagou: Benefits and risks of deferiprone in iron overload in thalassaemia and other conditions. Drug Safety 26, 553-584 (2003)
6. Kontoghiorghes, G. J.: Iron mobilization from transferrin and non-transferrin bound iron by deferiprone. Implications in the treatment of thalassaemia, anaemia of chronic disease, cancer and other conditions. Hemoglobin 30, 183-200 (2006)
7. Kontoghiorghes, G. J., & A. Kolnagou: Molecular factors and mechanisms affecting iron and other metal excretion or absorption in health and disease. The role of natural and synthetic chelators. Curr Med Chem 12, 2695-2709 (2005) (Pubitemid 41601568)
8. Cai, L., X. K. Li, Y. Song, & M. G. Cherian: Essentiality, toxicology and chelation therapy of zinc and copper. Curr Med Chem 12, 2753-2763 (2005) (Pubitemid 41601572)
9. Kontoghiorghes, G. J., E. Eracleous, C. Economides, & A. Kolnagou: Advances in iron overload therapies. Prospects for effective use of deferiprone (L1), deferoxamine, the new experimental chelators ICL670, GT56-252, L1NAll and their combination. Curr Med Chem 12, 2663-2681 (2005) (Pubitemid 41601566)
10. Kyriacou, K. Y., Michaelides, R. Senkus, K. Simamonian, N. Pavlides, L. Antoniades, & C. Zambartas: Ultrastructural pathology of the heart in patients with beta-thalassaemia major. Ultrastruct Pathol 24, 75-81 (2000) (Pubitemid 30241158)
11. Iancu, T. C., & H. B. Neustein: Ferritin in human liver cells of homozygous beta-thalassaemia: ultrastructural observations. Br J Haematol 37, 527-535 (1977) (Pubitemid 8273158)
12. Blanusa, M., V. M. Varnai, M Piasek, & K. Kostial: Chelators as antidotes of metal toxicity: therapeutic and experimental aspects. Curr Med Chem 12, 2771-2794 (2005) (Pubitemid 41601574)
13. Sargent, P. J., S. Farnaud, & R. W. Evans: Structure/function overview of proteins involved in iron storage and transport. Curr Med Chem 12, 2683-2693 (2005) (Pubitemid 41601567)
14. Sheppard, L., & G. J. Kontoghiorghes: Competition between deferipone, desferrioxamine and other chelators for iron and the effect of other metals. Arzheim-Forsch/Drug Res 43:659-663 (1993)
15. Pippard, M. J., M. J. Jackson, K. Hoffman, M. Petrou & C. B. Modell: Iron chelation using subcutaneous infusion of diethylene triamine penta-acetic acid (DTPA). Scand J Haematol 36, 466-472 (1986) (Pubitemid 16096161)
16. De Virgilis, S., M. Cognia, M. P. Turco, F. Frau, C. Dessi, F. Argiolou, R. Sorcinelli, A. Sitzia, & A. Cao: Depletion of trace elements and acute occular toxicity induced by desferrioxamine in patients with thalassaemia. Arch Dis Child, 250-255 (1988) (Pubitemid 18094662)
17. AlRefai, F. N., B. Wonke, D. G. Wickens, Y. Aydinok, A. Fielding, & A. V. Hoffbrand: Zinc concentration in patients with iron overload receiving oral iron chelator 1, 2-dimethyl-3-hydroxypyrid-4-one or desferrioxamine. J Clin Pathol 47:657-660 (1994)
18. Yamamoto, R. S., G. M. Williams, H. H. Frangel, & J. H. Weisburger: 8-hydroxyquinoline: chronic toxicity and inhibitory effect on the carcinogenicity of N-2-fluorenylacetamide. Toxicol Appl Pharmacol 19, 687-698 (1971)
19. Mostert, L. J., J. A. L. M. Van Dorst, J. F. Koster, H. G. Van Eijk, & G. J. Kontoghiorghes: Free radical and cytotoxic effects of chelators and their iron complexes in the hepatocyte. Free Rad Res Comms 3:379-388 (1987)
20. Kontoghiorghes, G. J., J. Barr, & R. A. Baillod: Studies of aluminium mobilisation in renal dialysis patients using the oral chelator 1, 2-dimethyl-3-hydroxypyrid-4-one. Arzn. Forsch/Drug Res 44:522-526 (1994) (Pubitemid 24122314)
21. Kontoghiorghes, G. J., M. A. Aldouri, A. V. Hoffbrand, J. Barr, B. Wonke, T. Kourouklaris, & L. Sheppard: Effective chelation of iron in beta-thalassaemia with the oral chelator 1, 2-dimethyl-3-hydroxypyrid-4-one. Br Med J 295:1509-1512 (1987) (Pubitemid 18009747)
22. Kontoghiorghes, G. J.: Chelators affecting iron absorption in mice. Arzn. Forsch/Drug Res 40, 1332-1335 (1990)
23. Kontoghiorghes, G. J., M. I. Jackson, & J. Lunec: In vitro screening of iron chelators using models of free radical damage. Free Rad Res Comms 2:115-24 (1986)
24. Srichairatanakool, S., S. Ounjaijean, C. Thephinlap, U. Khansuwan, C. Phisalpong, & S. Fuchareon: Iron-chelating and free-radical scavenging activities in microwaveprocessed green tea in iron overload. Hemoglobin 30, 311-327 (2006) (Pubitemid 43977333)
25. Kontoghiorghes, G. J.: The design of orally active iron chelators for the treatment of thalassaemia. PhD thesis, University of Essex, Colchester UK. British Library Microfilm No D66194/86. 1982:1-243
26. Kontoghiorghes, G. J.: Design, properties and effective use of the oral chelator L1 and other α-ketohydroxypyridines in the treatment of transfusional iron overload in thalassaemia. Ann NY Acad Sci 612, 339-350 (1990)
27. Kontoghiorghes, G. J., K. Pattichis, K. Neocleous, & A. Kolnagou: The design and development of deferiprone (L1) and other iron chelators for clinical use: Targeting methods and application prospects. Curr Med Chem 11, 2161-2183 (2004) (Pubitemid 38967737)
28. Kontoghiorghes, G. J., L. Sheppard, & S. Chambers: New synthetic approach and iron chelation studies of 1-alkyl-2-methyl-3-hydroxypyrid-4-ones. Arz. Forsch/Drug Res 37, 1099-1102 (1987) (Pubitemid 17138961)
29. Pashalidis, I., & G. J. Kontoghiorghes: Molecular factors affecting the complex formation between deferiprone (L1) and Cu (II). Arz. Forsch/Drug Res 51, 998-1003 (2001)
30. Pashalidis, I., & G. J. Kontoghiorghes: Effective complex formation in the interaction of I, 2-dimethyl-3-hydroxypyrid-4-one (Deferiprone or L1) with Uranium (VI). J Rad Nuclear Chem 242, 181-184 (1999) (Pubitemid 29501140)
31. Kontoghiorghes, G. J.: Comparative efficacy and toxicity of desferrioxamine, deferiprone and other iron and aluminium chelating drugs. Toxicol Lett 80, 1-18 (1995)
32. Kontoghiorghes, G. J., J. G. Goddard, A. N. Bartlett, & L. Sheppard: Pharmacokinetic studies in humans with the oral iron chelator 1, 2-dimethyl-3-hydroxypyrid-4-one. Clin Pharmacol Therap 48, 255-261 (1990) (Pubitemid 20323651)
33. Kontoghiorghes, G. J., A. N. Bartlett, A. V. Hoffbrand, J. G. Goddard, L. Sheppard, J. Barr, & Nortey P: Long term trial with the oral chelator 1, 2-dimethyl-3-hydroxypyrid-4-one (L1). (I) Iron chelation and metabolic studies. Br J Haematol 76, 295-300 (1990) (Pubitemid 20342689)
34. Kontoghiorghes, G. J., A. N. Bartlett, L. Sheppard, J. Barr, & P. Nortey: Oral iron chelation therapy with deferiprone (L1): Monitoring of biochemical, drug and iron excretion changes. Arzn. Forsch/Drug Res 45:65-69 (1995)
35. Sheppard, L., & G. J. Kontoghiorghes: Synthesis and metabolism of L1 and other novel alphaketohydroxypyridine iron chelators and their metal complexes. Drugs Today 28(Suppl A):3-10 (1992) (Pubitemid 23038080)
36. Matsui, D., J. Klein, C. Hermann, V. Grunau, R. McClelland, D. Chung, P. StLouis, N. Olivieri, & G. Koren: Relationship between the pharmacokinetics and iron excretion pharmacodynamics of the new oral iron chelator 1, 2-dimethyl-3-hydroxypyrid-4-one in patients with thalassaemia. Clin Pharmacol Therap 50, 294-298 (1991)
37. 59Fe-labelling technique. Drugs Today 28(suppl. A):45-53 (1992) (Pubitemid 23038086)
38. Diav-Citrin, O., G. Atanackovic, & G. Koren: An investigation into variability in the therapeutic response to deferiprone in patients with thalassaemia major. Therap Drug Monitor 21, 74-81 (1999) (Pubitemid 29077457)
39. Kontoghiorghes, G. J.: Clinical use, therapeutic aspects and future potential of deferiprone in thalassaemia and other conditions of iron and other metal toxicity. Drugs Today 37, 23-35 (2001) (Pubitemid 32220402)
40. Evans, R. W., M. Sharma, W. Ogwang, K. J. Patel, A. N. Bartlett, & G. J. Kontoghiorghes: The effect of alphaketohydroxypyridine chelators on transferrin saturation in vitro and in vivo. Drugs Today. 28(Suppl A), 19-23 (1992) (Pubitemid 23038082)
41. Nielsen, P., R. Fischer, R. Engelhardt, P. Tondury, E. E. Gabbe, & G. E. Janka: Liver iron stores in patients with secondary haemochromatosis under iron chelation therapy with deferoxamine or deferiprone. Br J Haematol 9, 827-833 (1995)
42. N. F. Olivieri, G. Koren, D. Matsui, P. P. Liu, L. Blendy, R. Cameron, R. A. McClelland, D. and M. Templeton: Reduction of tissue iron stores and normalisation of serum ferritin during treatment with the oral iron chelator L1 in thalassaemia intermedia. Blood 79, 2741-2748 (1992)
43. Anderson, L. J., B. Wonke, E. Prescott, S. Holden, J. M. Walker, & D. J. Pennel: Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta-thalassaemia. Lancet 360, 516-520 (2002) (Pubitemid 35232104)
44. * or T2 for preventing heart disease in thalassaemia. Br J Haematol 127, 360-361 (2004)
45. Dresow, B., R. Fischer, P. Nielsen, E. E. Gabbe, & A. Piga: Effect of oral iron chelator L1 in iron absorption in man. Ann N Y Acad Sci 850, 466-468 (1998) (Pubitemid 28369806)
46. Kontoghiorghes, G. J., T. Bunce, & K. R. Bruckdorfer: Differentiation of the therapeutic and toxicological effects of iron and copper chelating drugs in relation to free radical toxicity. Toxicol Lett 78, 48-49 (1995)
47. Pope, E., M. Berkovitch, J. Klein, F. Fassos, & G. Koren: Salivary measurement of deferiprone concentrations and correlation with serum levels. Ther Drug Monitor 19, 95-97 (1997) (Pubitemid 28069004)
48. Hoffbrand, A. V., A. Bartlett, P. A. Veys, N. T. J. O'Connor, & G. J. Kontoghiorghes: Agranulocytosis and thrombocytopenia in a patient with Blackfan-Diamond anaemia during oral chelator trial. Lancet II: 457 (1989) (Pubitemid 19195999)
49. Loebstein, R., O. Diav-Citrin, & G. Atanackovic: Deferiprone-induced agranulocytosis: a critical review of five rechallenged cases. Clin Drug Invest 13, 345-349 (1997) (Pubitemid 27279636)
50. Kontoghiorghes, G. J., A. H. Bartlett, & A. V. Hoffbrand: Prospects for effective oral iron chelation therapy in man with 1, 2-dimethyl-3- hydroxypyrid-4-one and other alphaketohydroxypyridines. Prog Clin Biol Res 309, 107-114 (1989)
51. Agarwal, M. B., S. S. Gupta, C. Viswanathan, D. Vasandani, J. Ramanathan, N. Desai, R. R. Puniyani, & A. T. Chhablani: Long term assessment of efficacy and toxicity of L1 (1, 2-dimethyl-3-hydroxypyrid-4-one in transfusion dependent thalassaemia: Indian trial. Drugs Today, 28(Suppl A) 107-114 (1992) (Pubitemid 23038093)
52. Cohen, A. R., R. Galanello, A. Piga, A. Di Palma, C. Voullo, & F. Tricta: Safety profile of the oral iron chelator deferiprone: a multicentre study. Br J Haematol 108, 305-312 (2000) (Pubitemid 30143646)
53. Henter, J. I., & J. Karlen: Fatal agranulocytosis after deferiprone therapy in a child with Diamond-Blackfan anemia. Blood 109, 5157-5159 (2007) (Pubitemid 46890530)
54. Douvas, S. G., M. H. May, A. Kolnagou, & G. J. Kontoghiorghes: Effects on Mycobacterium avium replication in normal human macrophages by deferiprone (L1) and other iron chelators. Possible implications on toxicity. Arzn. Forsch/Drug Res 52, 45-52 (2002) (Pubitemid 34084493)
55. Reeder, B. J., & M. T. Wilson: Hemoglobin and myoglobin associated oxidative stress: from molecular mechanisms to disease states. Curr Med Chem 12, 2741-2751 (2005) (Pubitemid 41601571)
56. Saleem, M. M., & M. T. Wilson: Kinetic studies on the reduction of cytochrome c. Reaction with dihydroxyconjugated compounds (catechols and quinols). Biochem J 20, 433-444 (1982)
57. Kontoghiorghes, G. J.: Orally active α-ketohydroxypyridine iron chelators. Effects on iron and other metal mobilisations. Acta Haematol 78, 212-236 (1987)
58. Moridani, M. Y., & P. J. O'Brien: Iron complexes of deferiprone and dietary plant catechols as cytoprotective superoxide radical scavengers. Biochem Pharmacol 62, 1579-1585 (2001) (Pubitemid 34033643)
59. Chakraborty, D., & M. Bhattacharrya: Deferiprone (L1) induced conformation change of hemoglobin: A fluorescence and CD spectroscopic study. Mol Cell Biochem 204, 17-20 (2000) (Pubitemid 30111753)
60. Korkina, L., C. De Luca, I. Deeva, S. Perrota, B. Nobili, P. Passi, & P. Puddui: L1 effects on reactive oxygen (ROS) and nitrogen species (RNS) release, haemoglobin oxidation, low molecular weight antioxidants, and antioxidant enzyme activities in red and white blood cells of thalassaemic patients. Transfus Sc 23, 253-254 (2000)
61. Tsukamoto, H.: Iron regulation of hepatic macrophage TNFalpha expression. Free Radic Biol Med 32, 309-313 (2002) (Pubitemid 34159084)
62. Van, A. M. M., der Kraaij, H. G. Van Eijk, & J. F. Koster: Prevention of postischemic cardiac injury by the orally active iron chelator 1, 2-dimethyl-3-hydroxy-4-pyridone (L1) and the antioxidant (+)-cyanidanol-3. Circulation 80, 158-164 (1989) (Pubitemid 19178649)
63. Barnabe, N., J. A. Zastre, S. Venkataram, & B. B. Hassinof.: Deferiprone protects against doxorubicin-induced myocyte cytotoxicity. Free Rad Biol Med 33, 266-275 (2002) (Pubitemid 34775198)
64. Hanauske-Abel, H. M., T. A. McCaffrey, & R. Grady: Protein hydroxylation inhibitors for fibroproliferative disorders. WO 9622021
65. Jeremy, J. Y., G. J. Kontoghiorghes, A. V. Hoffbrand, & P. Dandona: The iron chelators desferrioxamine and 1-alkyl-methyl-3-hydroxypyrid-4-ones inhibit vascular prostacylin synthesis in vitro. Biochem J. 254, 239-244 (1988)
66. Barradas, M. A., J. Jeremy, G. J. Kontoghiorghes, D. P. Michailidis, A. V. Hoffbrand, & P. Dandona: Iron chelators inhibit human platelet aggregation, thromboxane A synthesis and lipoxygenase activity. FEBS Lett 245, 105-109 (1989) (Pubitemid 19076212)
67. Sadrzadeh, S. M., A. A. Nanji, & P. L. Price: The oral iron chelator, 1, 2-dimethyl-3-hydroxypyrid-4-one reduces hepatic-free iron, lipid peroxidation and fat accumulation in chronically ethanol-fed rats. J Pharmacol Exp Ther 269, 632-636 (1994) (Pubitemid 24157331)
68. Crosland, R. D.: Action of reactive oxygen species and their antagonists on twitch tension of the rat phrenic nervediaphragm. Pharmacol Toxicol 77, 231-237 (1995)
69. Arthur, A. S., A. H. Fergus, G. Lanzino, J. Mathys, N. F. Kassell, & K. S. Lee: Systemic administration of the iron chelator deferiprone attenuates subarachnoid hemorrhageinduced cerebral vasospasm in the rabbit. Neurosurgery 41, 1385-1391 (1997)
70. J. Ablin, O. Shalev, E. Okon, F. Karmeli and D. Rachmilewitz: Deferiprone, an oral iron chelator, ameliorates experimental colitis and gastric ulceration in rats. Inflamm Bowel Dis 5, 253-261 (1999)
71. Waldmeier, P. C., A. M. Buchle, & A. F. Steulet: Inhibition of catechol-O-methyltransferase (COMT) as well as tyrosine and tryptophan hydroxylase by the orally active iron chelator, 1, 2-dimethyl-3-hydroxypyridin- 4-one (L1, CP20), in rat brain in vivo. Biochem Pharmacol 45, 2417-2424 (1993) (Pubitemid 23189534)
72. Eybl, V., D. Kotyzova, M. Kolek, J. Koutensky, & P. Nielsen: The influence of deferiprone (L1) and deferoxamine on iron and essential element tissue level and parameters of oxidative status in dietary iron-loaded mice. Toxicol Lett 128, 169-175 (2002) (Pubitemid 34183459)
73. Lai, H., & N. P. Singh: Magnetic-field-induced DNA strand breaks in brain cells of the rat. Environ Health Perspect 112, A726 (2004)
74. Xu, L. J., L. Jin, H. Pan, A. Z., G. Wei, P. P. Li, & W. Y. Lu: Deferiprone protects the isolated atria from cardiotoxicity induced by doxorubicin. Acta Pharmacol Sin 27, 1333-1339 (2006) (Pubitemid 44439968)
75. Mitchell, K. M., A. L. Dotson, K. M. Cool, A. Chakraparty, S. H. Benedict, & S. M. Levine: Deferiprone, an orally deliverable iron chelator, ameliorates experimental autoimmune encephalomyelitis. Mult Scler 13, 1118-1126 (2007) (Pubitemid 351541415)
76. Gorman, N., A. Zaharia, H. S. Trask, J. G. Szakacs, N. J. Jacobs, J. M. Jacobs, D. Balestra, J. F. Sinclair, & P. R. Sinclair: Effect of an oral iron chelator or iron-deficient diets on uroporphyria in a murine model of porphyria cutanea tarda. Hepatology 46, 1927-1034 (2007)
77. Matthews, A. J., G. M. Vercellotti, H. J. Menchaca P. H. Bloch, V. N. Michalek, P. H. Marker, & J. Murarand H. Buchwald: Iron and atherosclerosis: Inhibition by the iron chelator deferiprone (L1). J Surg Res 73, 35-40 (1997) (Pubitemid 28068315)
78. Kontoghiorghes, G. J., M. A. Aldouri, L. N. Sheppard, & A. V. Hoffbrand: 1, 2-Dimethyl-3-hydroxypyrid-4-one, on orally active chelator for the treatment of transfusional iron overload. Lancet I, 1294-1295 (1987) (Pubitemid 17072195)
79. Kolnagou, A., & G. J. Kontoghiorghes: Effective combination therapy of deferiprone and deferoxamine for the rapid clearance of excess cardiac iron and prevention of heart disease in thalassaemia. The protocol of the international committee on oral chelators. Hemoglobin 30, 239-249 (2006) (Pubitemid 43977326)
80. * validation and utility. Lancet 361, 184 (2003)
81. Vreugdenhil, G., G. J. Kontoghiorghes, H. G. Van Eijk, & A. J. G.: Swaak. Impaired erythropoietin responsiveness to the anemia in rheumatoid arthritis. A possible inverse relationship with iron stores and effects of the oral iron chelator 1, 2-dimethyl-3-hydroxypyrid-4-one. Clin Exp Rheumatol 9, 35-40 (1991)
82. Vreughtenhil, G., G. J. Kontoghiorghes, H. G. Van Eijk, & A. J. G. Swaak: Efficacy and safety of the oral chelator L1 in anaemic rheumadoit arthritis patients. Lancet II, 1398-1399 (1989) (Pubitemid 20003012)
83. Boddaert N., K. H. Le Quan Sang, A. Rotig, A. Leroy-Willig, S. Gallet, F. Brunelle, D. Sidi, J. C. Thalabard, A. Munnich, & Z. I. Cabantchik: Selective iron chelation in Friedreich ataxia: biologic and clinical implications. Blood 110, 401-408 (2007) (Pubitemid 47026862)
84. Rajapurkar, M. M., R. Beliga, & S. Shah: Treatment of patients with glomerulonephritis with an oral iron chelator. J Am Soc Nephrol 18, 57-58A (2007)
85. Rajapurkar, M. M., M. G. Alam, A. Bhattacharya, & S. Shah: Novel treatment for diabetic nephropathy. J Am Soc Nephrol 18, 329A (2007)
86. Britton, R. S., K. L. Leicester, & B. R. Bacon.: Iron toxicity and chelation therapy. Int J Haematol 76, 219-228 (2002) (Pubitemid 43020310)
87. Kolnagou, A., Y. Michaelids, C. Kontos, K. Kyriacou, & G. J. Kontoghiorghes: Myocyte damage and loss of myofibers is the potential mechanism of iron overload toxicity in congestive cardiac failure in thalasssaemia. Complete reversal of the cardiomyopathy and normalisation of iron load by deferiprone. Hemoglobin 32, 17-28 (2008) (Pubitemid 351264514)
88. Breuer, W., C. Hershko, & Z. I. Cabantchik: The importance of non-transferrin bound iron in disorders of iron metabolism. Transf Sc 23, 185-192 (2000)
89. Filosa, A., L. Valgimigli, G. F. Pedulli, A. Sapone, A. Maggio, D. Renda, C. Scazzone, R. Malizia, L. Pitrolo, C. Lo Pinto, Z. Borsellino, L. Cuccia, M. Capra, D. Canistro, M. Broccoli, A. Soleti, & M. Paolini: Quantitative evaluation of oxidative stress status on peripheral blood in beta-thalassaemic patients by means of electron paramagnetic resonance spectroscopy. Br J Haematol 131, 135-140 (2005) (Pubitemid 43899719)
90. Bartfay, W. J., D. C. Lehotay, G. D. Sher, E. Bartfay, B. Tyler, X. Luo, & P. P. Liu: Erythropoiesis: Comparison of Cytotoxic Aldehyde Generation in Beta-Thalassemia Patients Chelated with Deferoxamine or Deferiprone (L1) Versus NO Chelation. Hepatology 4, 67-76 (1999) (Pubitemid 29484062)
91. Platis, O., G. Anagnostopoulos, K. Farmaki, M. Posantzis, E. Gotsis, & G. Tolis: Glucose metabolism disorders improvement in patients with thalassaemia major after 24-36 months of intensive chelation therapy. Pediatr Endocrinol Rev 2, 279-281 (2004)
92. Lodi, R., P. E. Hart, B. Rajagopalana, D. J. Taylor, J. D. Grilley, J. L. Bradley, A. M. Blamire, D. Manners, P. Styles, A. H. Schapira, & J. M. Cooper: Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in patients with Friedreich's ataxia. Ann Neurol 49:590-596 (2001) (Pubitemid 32429786)
93. Koeppen, A. H., & A. C. Dickson: Iron in the Hallervorden-Spatz syndrome. Pediatric Neurolog. 25, 148-155 (2001) (Pubitemid 32830164)
94. Pootrakul, P., P. Sirankapracha, J. Sankote, U. Kachintorn, W. Maunqsub, K. Sriphen, K. Thakernpol, K. Atisuk, S. Fuchareon, U. Chantraluksri, O. Shalev, & A. V. Hoffbrand: Clinical trial of deferiprone iron chelation therapy in beta-thalassaemia/haemoglobin E patients in Thailand. Br J Haematol 122, 305-310 (2003) (Pubitemid 36859618)
95. th international conference on chelation (ICOC) for the treatment of thalassemia, cancer and other diseases related to metal and free radical imbalance and toxicity. Absrtract, p47, (2007)
96. th international conference on chelation (ICOC) for the treatment of thalassemia, cancer and other diseases related to metal and free radical imbalance and toxicity. Absrtract, p33, (2007)