Iron chelators and iron toxicity

Brittenham, Gary M.

doi:10.1016/s0741-8329(03)00101-0

Cited by 54Iron Metabolism and DisordersAlcohol Consumption and Health EffectsDrug-Induced Hepatotoxicity and Protection

Iron chelators and iron toxicity

Brittenham, Gary M.·2003·Alcohol

DOI 10.1016/s0741-8329(03)00101-0

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Abstract

Iron chelation may offer new approaches to the treatment and prevention of alcoholic liver disease. With chronic excess, either iron or alcohol alone may individually injure the liver and other organs. In combination, each exaggerates the adverse effects of the other. In alcoholic liver disease, both iron and alcohol contribute to the production of hepatic fibrosis through their effects on damaged hepatocytes, hepatic macrophages, hepatic stellate cells, and the extracellular matrix. The pivotal role of iron in these processes suggests that chelating iron may offer a new approach to arresting or ameliorating liver injury. For the past four decades, deferoxamine B mesylate has been the only iron-chelating agent generally available for clinical use. Clinical experience with deferoxamine has demonstrated the safety and effectiveness of iron chelation for the prevention and treatment of iron overload. Determined efforts to develop alternative agents have at last resulted in the development of a variety of candidate iron chelators that are now in or near clinical trial, including (a) the hexadentate phenolic aminocarboxylate HBED [N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid], (b) the tridentate desferrithiocin derivative 4'-OH-dadmDFT [4'-hydroxy-(S)-desazadesmethyl-desferrithiocin; (S)-4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-thiazolecarboxylic acid], (c) the tridentate triazole ICL670A [CGP72 670A; 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid], and (d) the bidentate hydroxypyridin-4-one deferiprone [L1, CP20; 1,2-dimethyl-3-hydroxypyridin-4-one]. These agents may provide new pharmacological means of averting or ameliorating liver damage in alcoholic liver disease by binding, inactivating, and eliminating the reactive forms of iron that contribute to oxidative injury of cellular components, are involved in signal transduction, or both.

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In alcoholic liver disease, both iron and alcohol contribute to the production of hepatic fibrosis.
“Specifically, in alcoholic liver disease, both iron and alcohol contribute to the production of hepatic fibrosis [1352-1358].”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [1353]

Hepcidin, a urinary antimicrobial peptide synthesized in the liver
Park, C. H., Valore, E. V., Waring, A. J., & Ganz, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008922200 · Cited by 2,168 · see citing works
Hematology: Basic Principles and Practice
(1991) · Annals of Internal Medicine · doi:10.7326/0003-4819-115-3-238_2 · Cited by 1,862 · see citing works
A New Mouse Liver-specific Gene, Encoding a Protein Homologous to Human Antimicrobial Peptide Hepcidin, Is Overexpressed during Iron Overload
Pigeon, C., Ilyin, G., Courselaud, B., Leroyer, P., Turlin, B., Brissot, P., & Loréal, O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008923200 · Cited by 1,697 · see citing works
Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 ( <i>USF2</i> ) knockout mice
Nicolas, G., Bennoun, M., Devaux, I., Beaumont, C., Grandchamp, B., Kahn, A., & Vaulont, S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151179498 · Cited by 1,233 · see citing works
The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation
Nicolas, G., Chauvet, C., Viatte, L., Danan, J. L., Bigard, X., Devaux, I., Beaumont, C., Kahn, A., & Vaulont, S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215686 · Cited by 1,214 · see citing works
Iron-Chelating Therapy and the Treatment of Thalassemia
Olivieri, N. F., & Brittenham, G. M. (1997) · Blood · doi:10.1182/blood.v89.3.739 · Cited by 1,088 · see citing works
Self-citation
Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis
Roetto, A., Papanikolaou, G., Politou, M., Alberti, F., Girelli, D., Christakis, J., Loukopoulos, D., & Camaschella, C. (2003) · Nature Genetics · doi:10.1038/ng1053 · Cited by 860 · see citing works
Survival in Medically Treated Patients with Homozygous β-Thalassemia
Olivieri, N. F., Nathan, D. G., MacMillan, J. H., Wayne, A. S., Liu, P. P., McGee, A., Martin, M., Koren, G., & Cohen, A. R. (1994) · New England Journal of Medicine · doi:10.1056/nejm199409013310903 · Cited by 842 · see citing works
Efficacy of Deferoxamine in Preventing Complications of Iron Overload in Patients with Thalassemia Major
Brittenham, G. M., Griffith, P. M., Nienhuis, A. W., McLaren, C. E., Young, N. S., Tucker, E. E., Allen, C. J., Farrell, D. E., & Harris, J. W. (1994) · New England Journal of Medicine · doi:10.1056/nejm199409013310902 · Cited by 822 · see citing works
Self-citation
Chemistry and biology of eukaryotic iron metabolism
Aisen, P. (2001) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(01)00063-2 · Cited by 804 · see citing works
Hematology: Basic Principles and Practice
Simon, T. (2001) · Transfusion · doi:10.1046/j.1537-2995.2001.41091177.x · Cited by 745 · see citing works
Molecular Cloning of Transferrin Receptor 2
Kawabata, H., Yang, R., Hirama, T., Vuong, P. T., Kawano, S., Gombart, A. F., & Koeffler, H. P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.30.20826 · Cited by 646 · see citing works
SURVIVAL AND CAUSES OF DEATH IN THALASSAEMIA MAJOR
Zurlo, M., Stefano, P. D., Borgna‐Pignatti, C., Palma, A. D., Melevendi, C., Piga, A. G., Gregorio, F. D., Mg, B., & Terzoli, S. (1989) · The Lancet · doi:10.1016/s0140-6736(89)90264-x · Cited by 607 · see citing works
Experimental liver cirrhosis induced by alcohol and iron.
Tsukamoto, H., Horne, W., Kamimura, S., Niemelä, O. J., Parkkila, S., Ylä‐Herttuala, S., & Brittenham, G. M. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118077 · Cited by 512 · see citing works
Self-citation
Long-Term Safety and Effectiveness of Iron-Chelation Therapy with Deferiprone for Thalassemia Major
Olivieri, N. F., Brittenham, G. M., McLaren, C. E., Templeton, D. M., Cameron, R., MCCLELLAND, R. A., Burt, A. D., & Fleming, K. A. (1998) · New England Journal of Medicine · doi:10.1056/nejm199808133390701 · Cited by 418 · see citing works
Self-citation
Risk factors of fibrosis in alcohol-induced liver disease
Raynard, B., Balian, A., Fallik, D., Capron, F., Bédossa, P., Chaput, J., & Naveau, S. (2002) · Hepatology · doi:10.1053/jhep.2002.31782 · Cited by 387 · see citing works
Practical management of iron overload
Porter, J. B. (2001) · British Journal of Haematology · doi:10.1046/j.1365-2141.2001.03195.x · Cited by 380 · see citing works
Survival and Disease Complications in Thalassemia Major
Borgna‐Pignatti, C., Rugolotto, S., Stefano, P. D., Piga, A. G., Gregorio, F. D., Gamberini, M. R., SABATO, V., Melevendi, C., Cappellini, M. D., & VERLATO, G. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb10479.x · Cited by 340 · see citing works
Liver pathology in genetic hemochromatosis: A review of 135 homozygous cases and their bioclinical correlations
Deugnier, Y., Loréal, O., Turlin, B., Guyader, D., Jouanolle, H., Moirand, R., Jacquelinet, C., & Brissot, P. (1992) · Gastroenterology · doi:10.1016/0016-5085(92)90331-r · Cited by 310 · see citing works
Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation
Angelucci, E., Muretto, P., Nicolucci, A., BARONCIANI, D., Erer, B., Gaziev, J., Ripalti, M., Sodani, P., Tomassoni, S., Visani, G., et al. (2002) · Blood · doi:10.1182/blood.v100.1.17 · Cited by 309 · see citing works
Long-term outcome of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in high-risk β-thalassemia
Davis, B. A., & Porter, J. B. (2000) · Blood · doi:10.1182/blood.v95.4.1229.004k32_1229_1236 · Cited by 282 · see citing works
Transferrin receptor 2: Continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis
Fleming, R. E., Migas, M. C., Holden, C. C., Waheed, A., Britton, R. S., Tomatsu, S., Bacon, B. R., & Sly, W. S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.040548097 · Cited by 273 · see citing works
Design of clinically useful iron(III)‐selective chelators
Liu, Z. D., & Hider, R. C. (2002) · Medicinal Research Reviews · doi:10.1002/med.1027 · Cited by 266 · see citing works
C/EBPα Regulates Hepatic Transcription of Hepcidin, an Antimicrobial Peptide and Regulator of Iron Metabolism
Courselaud, B., Pigeon, C., Inoue, Y., Inoue, J., Gonzalez, F. J., Leroyer, P., Gilot, D., Boudjema, K., Guguen-Guillouzo, C., Brissot, P., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202653200 · Cited by 245 · see citing works
The development of iron chelators for clinical use
Ghio, A., & Crumbliss, A. L. (1995) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(95)90109-4 · Cited by 234 · see citing works
Hepatic iron stores and markers of iron overload in alcoholics and patients with idiopathic hemochromatosis
Chapman, R. W., Morgan, M. Y., Laulicht, M., Hoffbrand, A. V., & Sherlock, S. (1982) · Digestive Diseases and Sciences · doi:10.1007/bf01316575 · Cited by 203 · see citing works
Safety profile of the oral iron chelator deferiprone: a multicentre study
Cohen, Galanello, Piga, DiPalma, Vullo, & Tricta (2000) · British Journal of Haematology · doi:10.1046/j.1365-2141.2000.01866.x · Cited by 191 · see citing works
Lack of progressive hepatic fibrosis during long-term therapy with deferiprone in subjects with transfusion-dependent beta-thalassemia
Wanless, I. R. (2002) · Blood · doi:10.1182/blood-2002-01-0306 · Cited by 175 · see citing works
Iron reduction before and during interferon therapy of chronic hepatitis C: Results of a multicenter, randomized, controlled trial
Fontana, R. J., Israel, J., LeClair, P., Banner, B. F., Tortorelli, K., Grace, N. D., Levine, R. A., Fiarman, G. S., Thiim, M., Tavill, A. S., et al. (2000) · Hepatology · doi:10.1002/hep.510310325 · Cited by 165 · see citing works
New Multidentate Ligands. VI. Chelating Tendencies of N,N′-Di(2-hydroxybenzyl)ethylenediamine-N,N′-diacetic Acid
Eplattenier, F. L., Murase, I., & Martell, A. E. (1967) · Journal of the American Chemical Society · doi:10.1021/ja00980a019 · Cited by 158 · see citing works
ICL670A: a new synthetic oral chelator: evaluation in hypertransfused rats with selective radioiron probes of hepatocellular and reticuloendothelial iron stores and in iron-loaded rat heart cells in culture
Hershko, C., Konijn, A. M., Nick, H. P., Breuer, W. V., Cabantchik, Z. I., & Link, G. (2001) · Blood · doi:10.1182/blood.v97.4.1115 · Cited by 151 · see citing works
Stoffwechselprodukte von Actinomyceten. 27. Mitteilung. Über die Konstitution von Ferrioxamin B
Bickel, H., Hall, G. E., KELLER‐SCHIERLEIN, W., Prelog, V., Vischer, E., & Wettstein, A. (1960) · Helvetica Chimica Acta · doi:10.1002/hlca.19600430732 · Cited by 143 · see citing works
Liver iron is predictive of death in alcoholic cirrhosis: a multivariate study of 229 consecutive patients with alcoholic and/or hepatitis C virus cirrhosis: a prospective follow up study
Ganne‐Carrié, N., Christidis, C., Chastang, C., Ziol, M., Chapel, F., Imbert‐Bismut, F., Trinchet, J., Guettier, C., & Beaugrand, M. (2000) · Gut · doi:10.1136/gut.46.2.277 · Cited by 137 · see citing works
11 The toxic effects of desferrioxamine
Porter, J. B., & Huehns, E. R. (1989) · Baillière s Clinical Haematology · doi:10.1016/s0950-3536(89)80027-7 · Cited by 136 · see citing works
Role of iron in NF-kappa B activation and cytokine gene expression by rat hepatic macrophages
Lin, M., Rippe, R. A., Niemelä, O. J., Brittenham, G. M., & Tsukamoto, H. (1997) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1997.272.6.g1355 · Cited by 133 · see citing works
Self-citation
Ferrioxamine excretion in iron-loaded man
Pippard, M., St, C., & Finch, C. A. (1982) · Blood · doi:10.1182/blood.v60.2.288.288 · Cited by 130 · see citing works
Iron primes hepatic macrophages for NF-κB activation in alcoholic liver injury
Tsukamoto, H., Lin, M., Ohata, M., Giulivi, C., French, S. W., & Brittenham, G. M. (1999) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1999.277.6.g1240 · Cited by 121 · see citing works
Self-citation
Long term effects of phlebotomy on biochemical and histological parameters of chronic hepatitis C
Yano, M., Hayashi, H., Wakusawa, S., Sanae, F., Takikawa, T., Shiono, Y., Arao, M., Ukai, K., Ito, H., Watanabe, K., et al. (2002) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2002.05436.x · Cited by 112 · see citing works
Iron Excretion in Thalassaemia Major After Administration of Chelating Agents
Smith, R. S. (1962) · BMJ · doi:10.1136/bmj.2.5319.1577 · Cited by 96 · see citing works
INTESTINAL IRON ABSORPTION IN CHRONIC ALCOHOLICS
Duane, P., Raja, K. B., Simpson, R. J., & Peters, T. J. (1992) · Alcohol and Alcoholism · doi:10.1093/oxfordjournals.alcalc.a045289 · Cited by 93 · see citing works
Intravenous infusion pharmacokinetics of desferrioxamine in thalassaemic patients.
Lee, P., Mohammed, N., Marshall, L., Abeysinghe, R. D., Hider, R. C., Porter, J. B., & Singh, S. (1993) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)07467-7 · Cited by 92 · see citing works
Monitoring chelation therapy to achieve optimal outcome in the treatment of thalassaemia
Porter, J. B., & DAVIS, B. (2002) · Best Practice & Research Clinical Haematology · doi:10.1053/beha.2002.0214 · Cited by 91 · see citing works
Toxicity of oral iron chelator L1
Berdoukas, V. A., Bentley, P., Frost, H., et al. (1993) · The Lancet · doi:10.1016/0140-6736(93)92443-w · Cited by 87 · see citing works
Interrelationships of alcohol and iron in liver disease with particular reference to the iron‐binding proteins, ferritin and transferrin
Fletcher, L. M., Halliday, J. W., & Powell, L. W. (1999) · Journal of Gastroenterology and Hepatology · doi:10.1046/j.1440-1746.1999.01836.x · Cited by 84 · see citing works
Evaluation of desferrithiocin and its synthetic analogs as orally effective iron chelators
Bergeron, R. J., Wiegand, J., Dionis, J. B., Egli-Karmakka, M., Frei, J., Huxley‐Tencer, A., & PETER, H. H. (1991) · Journal of Medicinal Chemistry · doi:10.1021/jm00111a023 · Cited by 84 · see citing works
Heterozygotes for HFE mutations have no increased risk of advanced alcoholic liver disease
Grove, J., Daly, A. K., Burt, A. D., Guzail, M., James, O., Bassendine, M. F., & Day, C. P. (1998) · Gut · doi:10.1136/gut.43.2.262 · Cited by 82 · see citing works
Iron reduction and sustained response to interferon-alpha therapy in patients with chronic hepatitis C: results of an Italian multicenter randomized study
Fargion, S. R., Fracanzani, A. L., Rossini, A., Borzio, M., Riggio, O., Belloni, G., Bissoli, F., Ceriani, R., Ballare, M., Massari, M., et al. (2002) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2002.05705.x · Cited by 80 · see citing works
Haptoglobin Polymorphism and Body Iron Stores
Delanghe, J., & Langlois, M. R. (2002) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2002.035 · Cited by 76 · see citing works
Up-regulation of Transferrin Receptor Expression in Hepatocytes by Habitual Alcohol Drinking Is Implicated in Hepatic Iron Overload in Alcoholic Liver Disease
Suzuki, Y., Saito, H., Suzuki, M., Hosoki, Y., Sakurai, S., Fujimoto, Y., & Kohgo, Y. (2002) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2002.tb02698.x · Cited by 75 · see citing works
The Action of Nine Chelators on Iron-Dependent Radical Damage
Dean, R. T., & Nicholson, P. (1994) · Free Radical Research · doi:10.3109/10715769409147506 · Cited by 70 · see citing works
HBED: A Potential Alternative to Deferoxamine for Iron-Chelating Therapy
Bergeron, R. J., Wiegand, J., & Brittenham, G. M. (1998) · Blood · doi:10.1182/blood.v91.4.1446 · Cited by 66 · see citing works
Self-citation
The Iron Chelator L1 Potentiates Oxidative DNA Damage in Iron-Loaded Liver Cells
Cragg, L., Hebbel, R. P., Miller, W. J., Solovey, A., Selby, S. A., & Enright, H. (1998) · Blood · doi:10.1182/blood.v92.2.632 · Cited by 66 · see citing works
Deferoxamine pharmacokinetics
Porter, J. B. (2001) · Seminars in Hematology · doi:10.1016/s0037-1963(01)90061-7 · Cited by 62 · see citing works
Changing concepts in haemochromatosis
Powell, L. W. (1970) · Postgraduate Medical Journal · doi:10.1136/pgmj.46.534.200 · Cited by 58 · see citing works
Development of iron chelators for clinical use
Baker, E. (1992) · UWA Profiles and Research Repository (University of Western Australia) · Cited by 58 · see citing works
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.
Sadrzadeh, S. M. H., Nanji, A. A., & Price, P. L. (1994) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)38746-x · Cited by 58 · see citing works
Desazadesmethyldesferrithiocin Analogues as Orally Effective Iron Chelators
Bergeron, R. J., Wiegand, J., Weimar, W. R., Vinson, J. R. T., Bussenius, J., Yao, G. W., & McManis, J. S. (1998) · Journal of Medicinal Chemistry · doi:10.1021/jm980340j · Cited by 57 · see citing works
Effects of C-4 Stereochemistry and C-4‘ Hydroxylation on the Iron Clearing Efficiency and Toxicity of Desferrithiocin Analogues
Bergeron, R. J., Wiegand, J., McManis, J. S., McCosar, B. H., Weimar, W. R., Brittenham, G. M., & Smith, R. E. (1999) · Journal of Medicinal Chemistry · doi:10.1021/jm990058s · Cited by 57 · see citing works
Self-citation
Phenolic ethylenediamine derivatives: a study of orally effective iron chelators.
Hershko, C., Grady, R. W., & Link, G. (1984) · PubMed · Cited by 56 · see citing works
Spur cell anaemia and hepatic iron stores in patients with alcoholic liver disease undergoing orthotopic liver transplantation
Pascoe, A., Kerlin, P., Steadman, C. J., Clouston, A. D., Jones, D., Powell, L. W., Jazwinska, E. C., Lynch, S. V., & Strong, R. W. (1999) · Gut · doi:10.1136/gut.45.2.301 · Cited by 52 · see citing works
Monitoring chelation therapy to achieve optimal outcome in the treatment of thalassaemia
Porter, J. B. (2002) · Best Practice & Research Clinical Haematology · doi:10.1016/s1521-6926(02)90214-8 · Cited by 49 · see citing works
Is There A Threshold of Hepatic Iron Concentration That Leads To Cirrhosis in C282y Hemochromatosis?
Adams, P. C. (2001) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2001.03472.x · Cited by 48 · see citing works
Non‐Transferrin‐Bound Iron in Alcohol Abusers
de Feo, T. M., Fargion, S., Duca, L., Cesana, B. M., Boncinelli, L., Lozza, P., Cappellini, M. D., & Fiorelli, G. (2001) · Alcoholism: Clinical and Experimental Research · doi:10.1111/j.1530-0277.2001.tb02152.x · Cited by 48 · see citing works
HBED: The Continuing Development of a Potential Alternative to Deferoxamine for Iron-Chelating Therapy
Bergeron, R. J., Wiegand, J., & Brittenham, G. M. (1999) · Blood · doi:10.1182/blood.v93.1.370 · Cited by 45 · see citing works
Self-citation
HBED ligand: preclinical studies of a potential alternative to deferoxamine for treatment of chronic iron overload and acute iron poisoning
Bergeron, R. J., Wiegand, J., & Brittenham, G. M. (2002) · Blood · doi:10.1182/blood.v99.8.3019 · Cited by 43 · see citing works
Self-citation
Spur cell anemia and hepatic iron stores in patients with alcoholic liver disease undergoing orthotopic liver transplantation
Pascoe, A., Kerlin, P., Steadman, C. J., Clouston, A. D., Powell, L. W., Jazwinska, E. C., Lynch, S. V., & Strong, R. W. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)85357-2 · Cited by 43 · see citing works
Iron regulation of hepatic macrophage TNFα expression1,2 1Guest editor: Arthur Cederbaum 2This article is part of a series of reviews on “Alcohol, Oxidative Stress and Cell Injury.” The full list of papers may be found on the homepage of the journal.
Tsukamoto, H. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00772-9 · Cited by 43 · see citing works
The controversial role of deferiprone in the treatment of thalassemia
Richardson, D. R. (2001) · Journal of Laboratory and Clinical Medicine · doi:10.1067/mlc.2001.114105 · Cited by 41 · see citing works
The role of cellular oxidases and catalytic iron in the pathogenesis of ethanol-induced liver injury
Shaw, S., & Jayatilleke, E. (1992) · Life Sciences · doi:10.1016/0024-3205(92)90570-f · Cited by 39 · see citing works
Results from a Phase I Clinical Trial of HBED
Grady, R. W., Hilgartner, M. W., Giardina, P. J., & Salbe, A. D. (1994) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-2554-7_37 · Cited by 36 · see citing works
Multifunctional antioxidant activity of HBED iron chelator
Samuni, A. M., Afeworki, M., Stein, W., et al. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00459-7 · Cited by 34 · see citing works
Chelator‐induced iron excretion in iron‐overloaded marmosets
Sergejew, T., Forgiarini, P., & Schnebli, H. (2000) · British Journal of Haematology · doi:10.1046/j.1365-2141.2000.02260.x · Cited by 33 · see citing works
Chronic hepatitis C treated with phlebotomy alone: biochemical and histological outcome
Sartori, M. (2001) · Digestive and Liver Disease · doi:10.1016/s1590-8658(01)80072-4 · Cited by 32 · see citing works
Assessment of the effect of the oral iron chelator deferiprone on asymptomatic Plasmodium falciparum parasitemia in humans.
Thuma, P. E., Olivieri, N. F., Mabeza, G. F., Biemba, G., Parry, D., Zulu, S., Fassos, F. F., MCCLELLAND, R. A., Koren, G., Brittenham, G. M., et al. (1998) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.1998.58.358 · Cited by 32 · see citing works
Self-citation
Anemia and iron kinetics in alcoholism.
Me, C., & Barton, J. C. (1980) · PubMed · Cited by 32 · see citing works
Desferrithiocin is an effective iron chelator in vivo and in vitro but ferrithiocin is toxic
Baker, E., Wong, A., Peter, H., & Jacobs, A. (1992) · British Journal of Haematology · doi:10.1111/j.1365-2141.1992.tb08251.x · Cited by 30 · see citing works
The Desferrithiocin Pharmacophore
Bergeron, R. J., Liu, C. Z., McManis, J. S., et al. (1994) · Journal of Medicinal Chemistry · doi:10.1021/jm00036a005 · Cited by 29 · see citing works
Iron overload in viral and alcoholic liver disease
Adams, P. C. (1998) · Journal of Hepatology · doi:10.1016/s0168-8278(98)80370-x · Cited by 27 · see citing works
Development and evaluation of the improved iron chelating agents EHPG, HBED and their dimethyl esters.
Hershko, C., Grady, R. W., & Link, G. (1984) · PubMed · Cited by 15 · see citing works
An Investigation of Desferrithiocin Metabolism
Bergeron, R. J., Wollenweber, M., & Wiegand, J. (1994) · Journal of Medicinal Chemistry · doi:10.1021/jm00044a009 · Cited by 10 · see citing works
Iron-related indexes in chronic alcoholics. Effect of alcohol withdrawal.
Conte, D., Corsetti, M., Colli, A., et al. (1998) · PubMed · Cited by 7 · see citing works
[Present aspects of the treatment of hemochromatosis (apropos of 100 observations)].
Darnis, F., Mosse, A., Breauté, C., et al. (1971) · PubMed · Cited by 1 · see citing works
Deferiprone: new preparation. Poorly assessed.
(2000) · PubMed · Cited by 1 · see citing works

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The Evolution of Iron Chelators for the Treatment of Iron Overload Disease and Cancer
Kalinowski, D. S., & Richardson, D. R. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.4.2 · Cited by 721 · see citing works
Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases
Kell, D. B. (2009) · BMC Medical Genomics · doi:10.1186/1755-8794-2-2 · Cited by 554 · see citing works
Role of iron in hepatic fibrosis: One piece in the puzzle
Philippe, M. A. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.v13.i35.4746 · Cited by 95 · see citing works

Comparison of Deferoxamine, Deferiprone and Deferasirox Iron-Chelating Agents in Reducing Serum Ferritin Levels in Patients with Thalassemia Major
Arya, A., Jokar, S., Etemadfar, P., et al. (2020) · Journal of Clinical Care and Skills · doi:10.52547/jccs.1.4.189 · Cited by 7 · see citing works
EE148 Canadian Cost-Effectiveness Analysis of Deferiprone Compared to Deferoxamine and Deferasirox for the Treatment of Iron Overload in Patients With Sickle Cell Disease and Other Anemias
Azimpour, K., Ramjee, L., Tremblay, G., et al. (2022) · Value in Health · doi:10.1016/j.jval.2022.09.400 · Cited by 1 · see citing works
Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes
Kontoghiorghe, C. N., & Kontoghiorghes, G. J. (2016) · DOAJ (DOAJ: Directory of Open Access Journals)
Comparison of iron chelation effects of deferoxamine, deferasirox, and combination of deferoxamine and deferiprone on liver and cardiac T2* MRI in thalassemia maior.
Ansari, S., Azarkeivan, A., Miri‐Aliabad, G., Yousefian, S., & Rostami, T. (2017) · Europe PMC (PubMed Central) · doi:10.22088/cjim.8.3.159 · Cited by 21 · see citing works
Current recommendations for chelation for transfusion‐dependent thalassemia
Kwiatkowski, J. L. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13088 · Cited by 46 · see citing works

Authors: Brittenham, G. M.
Affiliations: Columbia University Irving Medical Center (US)
Corresponding author: Brittenham, Gary M.
ORCID: Brittenham, Gary M.
Venue: Alcohol
Publisher: Elsevier BV
Published: 2003-06
Volume: 30
Issue: 2
Pages: 151-158
ISSN: 0741-8329 (ISSN-L)
DOI: 10.1016/s0741-8329(03)00101-0
OpenAlex: W2047521581
Cited by: 54
References: 83
Citations by year: 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 2
FWCI: 1.16
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Alcohol (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01hl062882-05)
National Heart, Lung, and Blood Institute (HL62882)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 49108, DK57209, R01DK057209, R01DK055462, DK55462)
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords: iron chelation, iron chelators, alcoholic liver disease, iron toxicity, deferoxamine, HBED, deferiprone, liver fibrosis, oxidative stress, iron overload, hepatoprotection
MeSH terms: Alcoholism, Clinical Trials as Topic, Humans, Iron, Iron Chelating Agents, Liver Cirrhosis, Alcoholic, Liver Diseases, Alcoholic, Iron Overload

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Iron chelators and iron toxicity

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