Iron Regulatory Proteins and Pharmacological Iron Modulators: Therapeutic Implications Iron Regulatory Proteins and Modulators
Trends in Peptide and Protein Sciences,
Vol. 9 No. 1 (2024),
31 January 2024
,
Page 1-10 (e5)
https://doi.org/10.22037/tpps.v9i1.46862
Abstract
Iron homeostasis in the human body is precisely regulated, primarily through the action of proteins such as hepcidin, produced by the liver. Hepcidin plays a crucial role in controlling iron release by binding to ferroportin, the exporter of iron from cells into circulation. Under normal conditions, absorbed iron effectively binds to transferrin for transport to various tissues. However, individuals with blood disorders requiring frequent blood transfusions are susceptible to iron overload. This condition arises because the body’s mechanisms for iron excretion become overwhelmed, leading to chronic accumulation of excess iron. Additionally, dysregulation of iron-related proteins, such as ferritin and transferrin receptors, can further complicate this imbalance in iron homeostasis. This review focused on iron hemostasis and the pharmacological treatments available for managing iron overload, with a particular focus on Deferoxamine and Deferasirox. These medications aim to chelate excess iron, promoting its excretion and alleviating the detrimental effects associated with chronic iron accumulation. By understanding the pathways and proteins involved in iron regulation, as well as the available treatment options, better strategies can be developed to address the challenges faced by patients with iron overload due to frequent blood transfusions.
HIGHLIGHTS
- Iron regulatory proteins are essential for maintaining iron homeostasis in the body.
- Iron overload, or hemochromatosis, occurs when the body accumulates excess iron.
- Iron overload leads to toxicity and potential damage to various organs.
- Deferoxamine is an injectable iron chelator that binds excess iron, facilitating its excretion.
- Deferasirox is an oral iron chelator for patients requiring long-term treatment of iron overload.
- Deferoxamine
- Deferasirox
- Hemostasis
- Iron

How to Cite
References
Agarwal, A.K. and J. Yee, (2019). "Hepcidin" Advances in Chronic Kidney Disease, 26(4): 298-305. DOI: http://dx.doi.org/https://doi.org/10.1053/j.ackd.2019.04.005.
Bedford, M.R., Ford, S.J., Horniblow, R.D., Iqbal, T.H. and C. Tselepis, (2013). "Iron chelation in the treatment of cancer: a new role for deferasirox?" The Journal of Clinical Pharmacology, 53(9): 885-891. DOI: http://dx.doi.org/https://doi.org/10.1002/jcph.113.
Brittenham Gary, M. (2011). "Iron-chelating therapy for transfusional iron overload" New England Journal of Medicine, 364(2): 146-156. DOI: http://dx.doi.org/10.1056/NEJMct1004810.
Cairo, G. and S. Recalcati, (2007). "Iron-regulatory proteins: molecular biology and pathophysiological implications." Expert Reviews in Molecular Medicine, 9(33): 1-13. DOI: http://dx.doi.org/10.1017/S1462399407000531.
Cappellini, M.D. and A. Taher, (2009). "Deferasirox (Exjade) for the treatment of iron overload." Acta Haematol, 122(2-3): 165-73. DOI: http://dx.doi.org/10.1159/000243801.
Carreau, N., Tremblay, D., Savona, M., Kremyanskaya, M. and J. Mascarenhas, (2016). "Ironing out the details of iron overload in myelofibrosis: Lessons from myelodysplastic syndromes." Blood Review, 30(5): 349-56. DOI: http://dx.doi.org/10.1016/j.blre.2016.04.003.
Chakurkar, V., Rajapurkar, M., Lele, S., Mukhopadhyay, B., Lobo, V., Injarapu, R., Sheikh, M., Dholu, B., Ghosh, A. and V. Jha, (2021). "Increased serum catalytic iron may mediate tissue injury and death in patients with COVID-19." Scientific Reports, 11(1): 19618. DOI: http://dx.doi.org/10.1038/s41598-021-99142-x.
Chalmers, A.W. and J.M. Shammo, (2016). "Evaluation of a new tablet formulation of deferasirox to reduce chronic iron overload after long-term blood transfusions." Therapeutics and Clinical Risk Management, 12: 201-208. DOI: http://dx.doi.org/10.2147/TCRM.S82449.
Charhon, S.A. (1990). "Deferoxamine therapy of aluminum toxicity in dialysis patients." In: de Broe, M. E. and J. W. Coburn (Eds.), Aluminum and Renal Failure, Dordrecht: Springer Netherlands, 309-323. PMID: 2357118.
Cheong, J.-W., Kim, H.-J., Lee, K.-H., Yoon, S.-S., Lee, J.H., Park, H.-S., Kim, H.Y., Shim, H., Seong, C.-M., Kim, C.S., Chung, J., Hyun, M.S., Jo, D.-Y., Jung, C.W., Sohn, S.K., Yoon, H.-J., Kim, B.S., Joo, Y.-D., Park, C.-Y. and Y.H. Min, (2014). "Deferasirox improves hematologic and hepatic function with effective reduction of serum ferritin and liver iron concentration in transfusional iron overload patients with myelodysplastic syndrome or aplastic anemia." Transfusion, 54(6): 1542-1551. DOI: http://dx.doi.org/https://doi.org/10.1111/trf.12507.
Chong, C.C., Redzuan, A.M., Sathar, J. and M. Makmor-Bakry, (2021). "Patient perspective on iron chelation therapy: barriers and facilitators of medication adherence." Journal of Patient Experience, 8: 2374373521996958. DOI: http://dx.doi.org/10.1177/2374373521996958.
Clara, C., Antonella, N. and S. Laura, (2020). "Iron metabolism and iron disorders revisited in the hepcidin era." Haematologica, 105(2): 260-272. DOI: http://dx.doi.org/10.3324/haematol.2019.232124.
Coates, T.D. and J.C. Wood, (2017). "How we manage iron overload in sickle cell patients." British Journal of Haematology, 177(5): 703-716. DOI: http://dx.doi.org/https://doi.org/10.1111/bjh.14575.
Crielaard, B.J., Lammers, T. and S. Rivella, (2017). "Targeting iron metabolism in drug discovery and delivery." Nature Reviews Drug Discovery, 16(6): 400-423. DOI: http://dx.doi.org/10.1038/nrd.2016.248.
Darwish, S.F., El-Bakly, W.M., El-Naga, R.N., Awad, A.S. and E. El-Demerdash, (2015). "Antifibrotic mechanism of deferoxamine in concanavalin A induced-liver fibrosis: Impact on interferon therapy." Biochemical Pharmacology, 98(1): 231-242. DOI: http://dx.doi.org/https://doi.org/10.1016/j.bcp.2015.09.001.
DeBenedictis, C.A., Raab, A., Ducie, E., Howley, S., Feldmann, J. and A.M. Grabrucker, (2020). "Concentrations of essential trace metals in the brain of animal species—a comparative study. " Brain Sciences, 10(7): 460. DOI: https://doi.org/10.3390/brainsci10070460.
Drakesmith, H., Nemeth, E. and T. Ganz, (2015). " Ironing out Ferroportin." Cell Metabolism, 22(5): 777-787. DOI: http://dx.doi.org/10.1016/j.cmet.2015.09.006.
Duck, K.A. and J.R. Connor, (2016). "Iron uptake and transport across physiological barriers." Biometals, 29(4): 573-91. DOI: http://dx.doi.org/10.1007/s10534-016-9952-2.
Eid, C., Hémadi, M., Ha-Duong, N.-T. and J.-M. El Hage Chahine, (2014). "Iron uptake and transfer from ceruloplasmin to transferrin." Biochimica et Biophysica Acta (BBA) - General Subjects, 1840(6): 1771-1781. DOI: http://dx.doi.org/https://doi.org/10.1016/j.bbagen.2014.01.011.
Entezari, S., Haghi, S.M., Norouzkhani, N., Sahebnazar, B., Vosoughian, F., Akbarzadeh, D., Islampanah, M., Naghsh, N., Abbasalizadeh, M. and N. Deravi, (2022). "Iron chelators in treatment of iron overload." Journal of Toxicology, 2022(1): 4911205. DOI: http://dx.doi.org/https://doi.org/10.1155/2022/4911205.
Farmakis, D., Giakoumis, A., Angastiniotis, M. and A. Eleftheriou, (2020). "The changing epidemiology of the ageing thalassaemia populations: A position statement of the thalassaemia international federation." European Journal of Haematology, 105(1): 16-23. DOI: http://dx.doi.org/https://doi.org/10.1111/ejh.13410.
Finkenstedt, A., Wolf, E., Höfner, E., Gasser, B.I., Bösch, S., Bakry, R., Creus, M., Kremser, C., Schocke, M., Theurl, M., Moser, P., Schranz, M., Bonn, G., Poewe, W., Vogel, W., Janecke, A.R. and H. Zoller, (2010). "Hepatic but not brain iron is rapidly chelated by deferasirox in aceruloplasminemia due to a novel gene mutation." Journal of Hepatology, 53(6): 1101-7. DOI: http://dx.doi.org/10.1016/j.jhep.2010.04.039.
Flora, S.J.S. and V. Pachauri, (2010). "Chelation in metal intoxication." International Journal of Environmental Research and Public Health, 7(7): 2745-2788. DOI: https://doi.org/10.3390/ijerph7072745.
Galy, B., Conrad, M. and M. Muckenthaler, (2024). "Mechanisms controlling cellular and systemic iron homeostasis." Nature Reviews Molecular Cell Biology, 25(2): 133-155. DOI: http://dx.doi.org/10.1038/s41580-023-00648-1.
Ganz, T. and E. Nemeth, (2012). "Hepcidin and iron homeostasis." Biochimica et Biophysica Acta (BBA) -Molecular Cell Research, 1823(9): 1434-1443. DOI: http://dx.doi.org/https://doi.org/10.1016/j.bbamcr.2012.01.014.
Gardenghi, S., Marongiu, M.F., Ramos, P., Guy, E., Breda, L., Chadburn, A., Liu, Y., Amariglio, N., Rechavi, G., Rachmilewitz, E.A., Breuer, W., Cabantchik, Z.I., Wrighting, D.M., Andrews, N.C., de Sousa, M., Giardina, P.J., Grady, R.W. and S. Rivella, (2007). "Ineffective erythropoiesis in β-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin." Blood, 109(11): 5027-5035. DOI: http://dx.doi.org/10.1182/blood-2006-09-048868.
Gattermann, N. (2018). "Iron overload in myelodysplastic syndromes (MDS)." International Journal of Hematology, 107(1): 55-63. DOI: http://dx.doi.org/10.1007/s12185-017-2367-1.
Gray, J.P. and S.D. Ray, (2023). "Chapter 17 - Side effects of metals and metal antagonists." In: Ray, S. D. (Ed.), Side Effects of Drugs Annual, Elsevier, pp. 217-225. DOI: https://doi.org/10.1016/bs.seda.2023.09.009.
Guo, Q., Li, L., Hou, S., Yuan, Z., Li, C., Zhang, W., Zheng, L. and X. Li, (2021). "The role of iron in cancer progression." Frontiers in Oncology, 11: 778492. DOI: http://dx.doi.org/10.3389/fonc.2021.778492.
Holden, P. and L.S. Nair, (2019). "Deferoxamine: an angiogenic and antioxidant molecule for tissue regeneration." Tissue Engineering Part B: Reviews, 25(6): 461-470. DOI: http://dx.doi.org/10.1089/ten.teb.2019.0111.
Hou, Z., Nie, C., Si, Z. and Y. Ma, (2013). "Deferoxamine enhances neovascularization and accelerates wound healing in diabetic rats via the accumulation of hypoxia-inducible factor-1α." Diabetes Research and Clinical Practice, 101(1): 62-71. DOI: http://dx.doi.org/https://doi.org/10.1016/j.diabres.2013.04.012.
Jia, P., Chen, H., Kang, H., Qi, J., Zhao, P., Jiang, M., Guo, L., Zhou, Q., Qian, N.D., Zhou, H.B., Xu, Y.J., Fan, Y. and L.F. Deng, (2016). "Deferoxamine released from poly(lactic-co-glycolic acid) promotes healing of osteoporotic bone defect via enhanced angiogenesis and osteogenesis." Journal of Biomedical Materials Research Part A, 104(10): 2515-2527. DOI: http://dx.doi.org/https://doi.org/10.1002/jbm.a.35793.
Jiang, X., Malkovskiy, A.V., Tian, W., Sung, Y.K., Sun, W., Hsu, J.L., Manickam, S., Wagh, D., Joubert, L.-M., Semenza, G.L., Rajadas, J. and M.R. Nicolls, (2014). "Promotion of airway anastomotic microvascular regeneration and alleviation of airway ischemia by deferoxamine nanoparticles." Biomaterials, 35(2): 803-813. DOI: http://dx.doi.org/https://doi.org/10.1016/j.biomaterials.2013.09.092.
Jones, G., Goswami, S.K., Kang, H., Choi, H.S. and J. Kim, (2020). "Combating iron overload: a case for deferoxamine-based nanochelators." Nanomedicine, 15(13): 1341-1356. DOI: http://dx.doi.org/10.2217/nnm-2020-0038.
Joshi, P.K., Patel, S.C., Shreya, D., Zamora, D.I., Patel, G.S., Grossmann, I., Rodriguez, K., Soni, M. and I. Sange, (2021). "Hereditary hemochromatosis: a cardiac perspective." Cureus, 13(11): e20009. DOI: http://dx.doi.org/10.7759/cureus.20009.
Kang, H., Han, M., Xue, J., Baek, Y., Chang, J., Hu, S., Nam, H., Jo, M.J., El Fakhri, G., Hutchens, M.P., Choi, H.S. and J. Kim, (2019). "Renal clearable nanochelators for iron overload therapy." Nature Communications, 10(1): 5134. DOI: http://dx.doi.org/10.1038/s41467-019-13143-z.
Kautz, L., Jung, G., Du, X., Gabayan, V., Chapman, J., Nasoff, M., Nemeth, E. and T. Ganz, (2015). "Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of β-thalassemia." Blood, 126(17): 2031-7. DOI: http://dx.doi.org/10.1182/blood-2015-07-658419.
Keberle, H. (1964). "The biochemistry of desferrioxamine and its relation to iron metabolism." Annals of the New York Academy of Sciences, 119(2): 758-768. DOI: http://dx.doi.org/https://doi.org/10.1111/j.1749-6632.1965.tb54077.x.
Kontoghiorghes, G.J. (2024). "The importance and essentiality of natural and synthetic chelators in medicine: increased prospects for the effective treatment of iron overload and iron deficiency." International Journal of Molecular Sciences, 25(9): 4654. DOI: https://doi.org/10.3390/ijms25094654.
Kontoghiorghes, G.J. and C.N. Kontoghiorghe, (2020). " Iron and chelation in biochemistry and medicine: new approaches to controlling iron metabolism and treating related diseases”, Cells, 9(6): 1456. DOI: https://doi.org/10.3390/cells9061456.
Kowdley, K.V., Gochanour, E.M., Sundaram, V., Shah, R.A. and P. Handa, (2021). "Hepcidin signaling in health and disease: ironing out the details." Hepatology Communications, 5(5): 723-735. DOI: https://doi.org/10.1002/hep4.1717.
Kowdley, K.V., Modi, N.B., Peltekian, K., Vierling, J.M., Ferris, C., Valone, F.H. and S. Gupta, (2023). "Rusfertide for the treatment of iron overload in HFE-related haemochromatosis: an open-label, multicentre, proof-of-concept phase 2 trial." The Lancet Gastroenterology & Hepatology, 8(12): 1118-1128. DOI: http://dx.doi.org/10.1016/S2468-1253(23)00250-9.
Kunireddy, N., Jacob, R., Khan, S.A., Yadagiri, B., Sai Baba, K.S.S., Rajendra Vara Prasad, I. and I.K. Mohan, (2018). "Hepcidin and ferritin: important mediators in inflammation associated anemia in systemic lupus erythematosus patients." Indian Journal of Clinical Biochemistry, 33(4): 406-413. DOI: http://dx.doi.org/10.1007/s12291-017-0702-1.
Lang, J., Zhao, X., Wang, X., Zhao, Y., Li, Y., Zhao, R., Cheng, K., Li, Y., Han, X., Zheng, X., Qin, H., Geranpayehvaghei, M., Shi, J., Anderson, G.J., Hao, J., Ren, H. and G. Nie, (2019). "Targeted co-delivery of the iron chelator deferoxamine and a HIF1α inhibitor impairs pancreatic tumor growth." ACS Nano, 13(2): 2176-2189. DOI: http://dx.doi.org/10.1021/acsnano.8b08823.
Lele, S., Shah, S., McCullough, P. and M. Rajapurkar, (2009). "Serum catalytic iron as a novel biomarker of vascular injury in acute coronary syndromes." EuroIntervention, 5(3): 336-342. DOI: https://doi.org/10.4244/v5i3a53.
Linder, G.E. and S.T. Chou, (2021). "Red cell transfusion and alloimmunization in sickle cell disease." Haematologica, 106(7): 1805-1815. DOI: http://dx.doi.org/10.3324/haematol.2020.270546.
Manduzio, P. (2015). "Deferasirox in a refractory anemia after other treatment options: case report and literature review." Clinical Case Reports, 3(6): 361-367. DOI: http://dx.doi.org/https://doi.org/10.1002/ccr3.262.
Marques, O., Weiss, G. and M.U. Muckenthaler, (2022). "The role of iron in chronic inflammatory diseases: from mechanisms to treatment options in anemia of inflammation." Blood, 140(19): 2011-2023. DOI: http://dx.doi.org/https://doi.org/10.1182/blood.2021013472.
Messa, E., Carturan, S., Maffè, C., Pautasso, M., Bracco, E., Roetto, A., Messa, F., Arruga, F., Defilippi, I., Rosso, V., Zanone, C., Rotolo, A., Greco, E., Pellegrino, R.M., Alberti, D., Saglio, G. and D. Cilloni, (2010). "Deferasirox is a powerful NF-kappaB inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging." Haematologica, 95(8): 1308-16. DOI: http://dx.doi.org/10.3324/haematol.2009.016824.
Miyake, Z., Nakamagoe, K., Yoshida, K., Kondo, T. and A. Tamaoka, (2020). "Deferasirox might be effective for microcytic anemia and neurological symptoms associated with aceruloplasminemia: a case report and review of the literature." Internal Medicine, 59(14): 1755-1761. DOI: http://dx.doi.org/10.2169/internalmedicine.4178-19.
Mobarra, N., Shanaki, M., Ehteram, H., Nasiri, H., Sahmani, M., Saeidi, M., Goudarzi, M., Pourkarim, H. and M. Azad, (2016). "A Review on iron chelators in treatment of iron overload syndromes." International Journal of Hematology- Oncology and Stem Cell Research, 10(4): 239-247. PMID: 27928480.
Modell, B., Khan, M. and M. Darlison, (2000). " Survival in β-thalassaemia major in the UK: data from the UK Thalassaemia Register." The Lancet, 355(9220): 2051-2052. DOI: http://dx.doi.org/https://doi.org/10.1016/S0140-6736(00)02357-6.
Moukalled, N.M., Bou-Fakhredin, R. and A.T. Taher, (2018). " Deferasirox: over a decade of experience in thalassemia. " Mediterranean Journal of Hematology and Infectious Diseases, 10(1): e2018066. DOI: http://dx.doi.org/10.4084/mjhid.2018.066.
Mu, Q., Chen, L., Gao, X., Shen, S., Sheng, W., Min, J. and F. Wang, (2021). " The role of iron homeostasis in remodeling immune function and regulating inflammatory disease." Science Bulletin, 66(17): 1806-1816. DOI: http://dx.doi.org/https://doi.org/10.1016/j.scib.2021.02.010.
Musallam, K.M., Barella, S., Origa, R., Ferrero, G.B., Lisi, R., Pasanisi, A., Longo, F., Gianesin, B. and G.L. Forni, (2024). "Differential effects of iron chelators on iron burden and long-term morbidity and mortality outcomes in a large cohort of transfusion-dependent β-thalassemia patients who remained on the same monotherapy over 10 years." Blood Cells, Molecules, and Diseases, 107: 102859. DOI: http://dx.doi.org/https://doi.org/10.1016/j.bcmd.2024.102859.
Nairz, M. and G. Weiss, (2020). "Iron in infection and immunity." Molecular Aspects of Medicine, 75: 100864. DOI: http://dx.doi.org/https://doi.org/10.1016/j.mam.2020.100864.
Norbert, G., Carlo, F., Matteo Della, P., Pierre, F., Michael, S., Agnes, G.-B., Mathias, S., Kerry, T., Dominique, V., Dany, H., Andrea, M., Bernard, R. and R. Christian, (2012). "Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes." Haematologica, 97(9): 1364-1371. DOI: http://dx.doi.org/10.3324/haematol.2011.048546.
Ohyashiki, J.H., Kobayashi, C., Hamamura, R., Okabe, S., Tauchi, T. and K. Ohyashiki, (2009). "The oral iron chelator deferasirox represses signaling through the mTOR in myeloid leukemia cells by enhancing expression of REDD1." Cancer Science, 100(5): 970-977. DOI: http://dx.doi.org/https://doi.org/10.1111/j.1349-7006.2009.01131.x.
Pan, T., Ji, Y., Liu, H., Tang, B., Song, K., Wan, X., Yao, W., Sun, G., Wang, J. and Z. Sun, (2023). "Impact of iron overload and iron chelation with deferasirox on outcomes of patients with severe aplastic anemia after allogeneic hematopoietic stem cell transplantation." Transplantation and Cellular Therapy, 29(8): 507.e1-507.e8. DOI: http://dx.doi.org/https://doi.org/10.1016/j.jtct.2023.04.016.
Piga, A., Longo, F., Origa, R., Roggero, S., Pinna, F., Zappu, A., Castiglioni, C. and M.D. Cappellini, (2014). "Deferasirox for cardiac siderosis in β-thalassaemia major: a multicentre, open label, prospective study." British Journal of Haematology, 167(3): 423-426. DOI: http://dx.doi.org/https://doi.org/10.1111/bjh.12987.
Pinto, V.M. and G.L. Forni, (2020). "Management of iron overload in beta-thalassemia patients: clinical practice update based on case series." International Journal of Molecular Sciences, 21(22): 8771. DOI: https://doi.org/10.3390/ijms21228771.
Porter, J.B. (2010). "Deferasirox—current knowledge and future challenges." Annals of the New York Academy of Sciences, 1202(1): 87-93. DOI: http://dx.doi.org/https://doi.org/10.1111/j.1749-6632.2010.05582.x.
Prabhune, N.M., Ameen, B. and S. Prabhu, (2024). "Therapeutic potential of synthetic and natural iron chelators against ferroptosis." Naunyn-Schmiedeberg”s Archives of Pharmacology. In press. DOI: http://dx.doi.org/10.1007/s00210-024-03640-4.
Prisciandaro, M., Adriatico, A., Lancia, A. and A. Marzocchella, (2013). "Thermodynamic equilibrium study of deferoxamine salting out crystallization." Chemical Engineering Transactions, 32: 2179-2184. DOI: https://doi.org/10.3303/CET1332364.
Puntarulo, S. (2005). "Iron, oxidative stress and human health." Molecular Aspects of Medicine, 26(4): 299-312. DOI: http://dx.doi.org/https://doi.org/10.1016/j.mam.2005.07.001.
Qin, Y., Li, G., Sun, Z., Xu, X., Gu, J. and F. Gao, (2019). "Comparison of the effects of nimodipine and deferoxamine on brain injury in rat with subarachnoid hemorrhage." Behavioural Brain Research, 367: 194-200. DOI: http://dx.doi.org/https://doi.org/10.1016/j.bbr.2019.04.004.
Rana, S. and N. Prabhakar, (2021). "Iron disorders and hepcidin." Clinica Chimica Acta, 523: 454-468. DOI: http://dx.doi.org/10.1016/j.cca.2021.10.032.
Renassia, C. and C. Peyssonnaux, (2019). "New insights into the links between hypoxia and iron homeostasis." Current Opinion in Hematology, 26(3): 125-130. DOI: http://dx.doi.org/10.1097/moh.0000000000000494.
Rivella, S. (2012). "The role of ineffective erythropoiesis in non-transfusion-dependent thalassemia." Blood Review, 26: S12-S15. DOI: http://dx.doi.org/https://doi.org/10.1016/S0268-960X(12)70005-X.
Roy, C.N. and C.A. Enns, (2000). "Iron homeostasis: new tales from the crypt." Blood, 96(13): 4020-4027. DOI: http://dx.doi.org/10.1182/blood.V96.13.4020.
Samara, A., Shapira, S., Lubin, I., Shpilberg, O., Avigad, S., Granot, G. and P. Raanani, (2021). "Deferasirox induces cyclin D1 degradation and apoptosis in mantle cell lymphoma in a reactive oxygen species- and GSK3β-dependent mechanism." British Journal of Haematology, 192(4): 747-760. DOI: http://dx.doi.org/https://doi.org/10.1111/bjh.17284.
Shah, N.R. (2017). "Advances in iron chelation therapy: transitioning to a new oral formulation." Drugs Context, 6: 212502. DOI: http://dx.doi.org/10.7573/dic.212502.
Shah, Y.M. and L. Xie, (2014). "Hypoxia-inducible factors link iron homeostasis and erythropoiesis." Gastroenterology, 146(3): 630-642. DOI: http://dx.doi.org/https://doi.org/10.1053/j.gastro.2013.12.031.
Shander, A., Cappellini, M.D. and L.T. Goodnough, (2009). "Iron overload and toxicity: the hidden risk of multiple blood transfusions." Vox Sanguinis, 97(3): 185-197. DOI: http://dx.doi.org/https://doi.org/10.1111/j.1423-0410.2009.01207.x.
Sleiman, J., Tarhini, A., Bou-Fakhredin, R., Saliba, A.N., Cappellini, M.D. and A.T. Taher, (2018). "Non-transfusion-dependent thalassemia: an update on complications and management." International Journal of Molecular Sciences, 19(1): 182. DOI: https://doi.org/10.3390/ijms19010182.
Steere, A.N., Byrne, S.L., Chasteen, N.D. and A.B. Mason, (2012). "Kinetics of iron release from transferrin bound to the transferrin receptor at endosomal pH." Biochimica et Biophysica Acta, 1820(3): 326-33. DOI: http://dx.doi.org/10.1016/j.bbagen.2011.06.003.
Strauss, W.E. and M. Auerbach, (2018). "Health-related quality of life in patients with iron deficiency anemia: impact of treatment with intravenous iron." Patient Related Outcome Measures, 9: 285-298. DOI: http://dx.doi.org/10.2147/PROM.S169653.
Stumpf, J.L. (2007). "Deferasirox." American Journal of Health-System Pharmacy, 64(6): 606-616. DOI: http://dx.doi.org/10.2146/ajhp060405.
Taher, A.T. and A.N. Saliba, (2017). " Iron overload in thalassemia: different organs at different rates." Hematology, 2017(1): 265-271. DOI: http://dx.doi.org/10.1182/asheducation-2017.1.265.
Tanaka, C. (2014). "Clinical pharmacology of Deferasirox." Clinical Pharmacokinetics, 53(8): 679-694. DOI: http://dx.doi.org/10.1007/s40262-014-0151-4.
Tanner, M.A., Galanello, R., Dessi, C., Smith, G.C., Westwood, M.A., Agus, A., Pibiri, M., Nair, S.V., Walker, J.M. and D.J. Pennell, (2008). "Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction." Journal of Cardiovascular Magnetic Resonance, 10(1): 12. DOI: http://dx.doi.org/10.1186/1532-429X-10-12.
Umemura, M., Kim, J.-H., Aoyama, H., Hoshino, Y., Fukumura, H., Nakakaji, R., Sato, I., Ohtake, M., Akimoto, T., Narikawa, M., Tanaka, R., Fujita, T., Yokoyama, U., Taguri, M., Okumura, S., Sato, M., Eguchi, H. and Y. Ishikawa, (2017). "The iron chelating agent, deferoxamine detoxifies Fe(Salen)-induced cytotoxicity." Journal of Pharmacological Sciences, 134(4): 203-210. DOI: http://dx.doi.org/https://doi.org/10.1016/j.jphs.2017.07.002.
Villalón-García, I., Povea-Cabello, S., Álvarez-Córdoba, M., Talaverón-Rey, M., Suárez-Rivero, J.M., Suárez-Carrillo, A., Munuera-Cabeza, M., Reche-López, D., Cilleros-Holgado, P., Piñero-Pérez, R. and J.A. Sánchez-Alcázar, (2023). "Vicious cycle of lipid peroxidation and iron accumulation in neurodegeneration." Neural Regeneration Research, 18(6): 1196-1202. DOI: https://doi.org/10.4103/1673-5374.358614.
Vogt, A.-C.S., Arsiwala, T., Mohsen, M., Vogel, M., Manolova, V. and M.F. Bachmann, (2021). "On iron metabolism and its regulation." International Journal of Molecular Sciences, 22(9): 4591. DOI: https://doi.org/10.3390/ijms22094591.
Wang, X., Li, Y., Han, L., Li, J., Liu, C. and C. Sun, (2021). "Role of flavonoids in the treatment of iron overload." Frontiers in Cell and Developmental Biology, 9: 685364. DOI: http://dx.doi.org/10.3389/fcell.2021.685364.
Xu, J., Sun, T., Zhong, R., You, C. and M. Tian, (2020). "PEGylation of deferoxamine for improving the stability, cytotoxicity, and iron-overload in an experimental stroke model in rats." Frontiers in Bioengineering and Biotechnology, 8: 592294. DOI: http://dx.doi.org/10.3389/fbioe.2020.592294.
Zhang, D.L., Senecal, T., Ghosh, M.C., Ollivierre-Wilson, H., Tu, T. and T.A. Rouault, (2011). "Hepcidin regulates ferroportin expression and intracellular iron homeostasis of erythroblasts." Blood, 118(10): 2868-77. DOI: http://dx.doi.org/10.1182/blood-2011-01-330241.
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