Deferoxamine Explained

Iupac Name:N--N-[5-({4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanoyl}amino)pentyl]-N-hydroxysuccinamide
Tradename:Desferal
Pregnancy Us:C
Elimination Half-Life:6 hours
Cas Number:70-51-9
Atc Prefix:V03
Atc Suffix:AC01
Pubchem:2973
Drugbank:DB00746
Chemspiderid:2867
Unii:J06Y7MXW4D
Kegg:D03670
Chebi:4356
Chembl:556
Synonyms:desferrioxamine B, desferoxamine B, DFO-B, DFB,N'-[5-(Acetyl-hydroxy-amino)pentyl]-N-[5-[3-(5-aminopentyl-hydroxy-carbamoyl) propanoylamino]pentyl]-N-hydroxy-butane diamide
C:25
H:48
N:6
O:8
Smiles:CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN
Stdinchi:1S/C25H48N6O8/c1-21(32)29(37)18-9-3-6-16-27-22(33)12-14-25(36)31(39)20-10-4-7-17-28-23(34)11-13-24(35)30(38)19-8-2-5-15-26/h37-39H,2-20,26H2,1H3,(H,27,33)(H,28,34)
Stdinchikey:UBQYURCVBFRUQT-UHFFFAOYSA-N

Deferoxamine (DFOA), also known as desferrioxamine and sold under the brand name Desferal, is a medication that binds iron and aluminium. It is specifically used in iron overdose, hemochromatosis either due to multiple blood transfusions or an underlying genetic condition, and aluminium toxicity in people on dialysis.[1] It is used by injection into a muscle, vein, or under the skin.

Common side effects include pain at the site of injection, diarrhea, vomiting, fever, hearing loss, and eye problems. Severe allergic reactions including anaphylaxis and low blood pressure may occur. It is unclear if use during pregnancy or breastfeeding is safe for the baby.[2] Deferoxamine is a siderophore from the bacteria Streptomyces pilosus.[3] [4]

Deferoxamine was approved for medical use in the United States in 1968.[5] It is on the World Health Organization's List of Essential Medicines.[6]

Medical uses

Deferoxamine is used to treat acute iron poisoning, especially in small children.[7] This agent is also frequently used to treat hemochromatosis, a disease of iron accumulation that can be either genetic or acquired. Acquired hemochromatosis is common in patients with certain types of chronic anemia (e.g. thalassemia and myelodysplastic syndrome) who require many blood transfusions, which can greatly increase the amount of iron in the body. Treatment with iron-chelating drugs such as deferoxamine reduces mortality in persons with sickle cell disease or β‐thalassemia who are transfusion dependent.[8]

Administration for chronic conditions is generally accomplished by subcutaneous injection over a period of 8–12 hours each day. Administration of deferoxamine after acute intoxication may color the urine a pinkish red, a phenomenon termed "vin rosé urine". Apart from iron toxicity, deferoxamine can be used to treat aluminium toxicity (an excess of aluminium in the body) in selected patients. In US, the drug is not FDA-approved for this use. Deferoxamine is also used to minimize doxorubicin's cardiotoxic side effects and in the treatment of patients with aceruloplasminemia.[9] Deferoxamine may be effective for improving neurologic outcomes in persons with intracranial hemorrhage, although the evidence supporting the efficacy and safety for this indication was weak.[10]

Some published manuscripts suggesting the use of deferoxamine for patients diagnosed with COVID-19 because of the high level of ferritin among them.[11] [12]

Adverse effects

It is unclear if use during pregnancy is safe for the baby.[2]

Chronic use of deferoxamine may increase the risk of hearing loss in patients with thalassemia major.[13]

Chronic use of deferoxamine may cause ocular symptoms, growth retardation, local reactions and allergy.[14]

Mechanism

Deferoxamine is produced by removal of the trivalent iron moiety from ferrioxamine B, an iron-bearing sideramine produced by the actinomycetes, Streptomyces pilosus. Its discovery was a serendipitous result of research conducted by scientists at Ciba in collaboration with scientists at the Swiss Federal Institute of Technology in Zurich and the University Hospital in Freiburg, Germany[15] [3] Deferoxamine acts by binding free iron in the bloodstream and enhancing its elimination in the urine. By removing excess iron from persons with hemochromatosis, the agent reduces the damage done to various organs and tissues, such as the liver. Also, it speeds healing of nerve damage (and minimizes the extent of recent nerve trauma). Deferoxamine may modulate expression[16] and release of inflammatory mediators by specific cell types.[17]

Research

Deferoxamine is being studied as a treatment for spinal cord injury[18] and intracerebral hemorrhage.[19] [20] It is also used to induce hypoxia-like environment in mesenchymal stem cells.[21] [22]

Since the terminal amine group of Deferoxamine does not participate in metal chelation, it has been used to immobilize Deferoxamine to surfaces and substrates for various industrial and biomedical applications.[23]

See also

Notes and References

  1. Book: WHO Model Formulary 2008 . 2009 . 9789241547659 . ((World Health Organization)) . Stuart MC, Kouimtzi M, Hill SR . 10665/44053 . World Health Organization . World Health Organization . free . 61–62 .
  2. Web site: Deferoxamine (Desferal) Use During Pregnancy. www.drugs.com. 13 December 2016. live. https://web.archive.org/web/20161221002833/https://www.drugs.com/pregnancy/deferoxamine.html. 21 December 2016.
  3. Book: Giardina PJ, Rivella S . Thalassemia Syndromes . Hoffman R, Benz Jr EJ, Silberstein LE, Heslop H, Weitz J, Anastasi J . Hematology: Diagnosis and Treatment. 2012. Elsevier Health Sciences. 978-1-4557-4041-3. 515. 6th. https://books.google.com/books?id=M5fD7gZSDYMC&pg=PA515. en. live. https://web.archive.org/web/20161220111527/https://books.google.ca/books?id=M5fD7gZSDYMC&pg=PA515. 2016-12-20.
  4. Keberle H . The Biochemistry of Desferrioxamine and its Relation to Iron Metabolism . Annals of the New York Academy of Sciences . 119 . 2 . 758–768 . October 1964 . 14219455 . 10.1111/j.1749-6632.1965.tb54077.x . 37277528 .
  5. Web site: Deferoxamine Mesylate. The American Society of Health-System Pharmacists. 8 December 2016. live. https://web.archive.org/web/20161221002616/https://www.drugs.com/monograph/deferoxamine-mesylate.html. 21 December 2016.
  6. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 21st list 2019 . 2019 . 10665/325771 . World Health Organization . World Health Organization . Geneva . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO . free .
  7. Merlot AM, Kalinowski DS, Richardson DR . Novel chelators for cancer treatment: where are we now? . Antioxidants & Redox Signaling . 18 . 8 . 973–1006 . March 2013 . 22424293 . 10.1089/ars.2012.4540 .
  8. Ballas SK, Zeidan AM, Duong VH, DeVeaux M, Heeney MM . The effect of iron chelation therapy on overall survival in sickle cell disease and β-thalassemia: A systematic review . American Journal of Hematology . 93 . 7 . 943–952 . July 2018 . 29635754 . 10.1002/ajh.25103 . free .
  9. Miyajima H, Takahashi Y, Kamata T, Shimizu H, Sakai N, Gitlin JD . Use of desferrioxamine in the treatment of aceruloplasminemia . Annals of Neurology . 41 . 3 . 404–407 . March 1997 . 9066364 . 10.1002/ana.410410318 . 22425032 .
  10. Zeng L, Tan L, Li H, Zhang Q, Li Y, Guo J . Deferoxamine therapy for intracerebral hemorrhage: A systematic review . PLOS ONE . 13 . 3 . e0193615 . 2018 . 29566000 . 5863956 . 10.1371/journal.pone.0193615 . free . 2018PLoSO..1393615Z .
  11. Abobaker A . Can iron chelation as an adjunct treatment of COVID-19 improve the clinical outcome? . European Journal of Clinical Pharmacology . 76 . 11 . 1619–1620 . November 2020 . 32607779 . 7325475 . 10.1007/s00228-020-02942-9 .
  12. Alkattan A, Alabdulkareem K, Kamel A, Abdelseed H, Almutairi Y, Alsalameen E . Correlation between Micronutrient plasma concentration and disease severity in COVID-19 patients. . Alexandria Journal of Medicine . January 2021 . 57 . 1 . 21–27 . 10.1080/20905068.2020.1870788 . 8108185 .
  13. Badfar G, Mansouri A, Shohani M, Karimi H, Khalighi Z, Rahmati S, Delpisheh A, Veisani Y, Soleymani A, Azami M . Hearing loss in Iranian thalassemia major patients treated with deferoxamine: A systematic review and meta-analysis . Caspian Journal of Internal Medicine . 8 . 4 . 239–249 . 2017 . 29201313 . 5686301 . 10.22088/cjim.8.4.239 .
  14. Taher AT, Musallam KM, Cappellini MD . β-Thalassemias . The New England Journal of Medicine . 384 . 8 . 727–743 . February 2021 . 33626255 . 10.1056/NEJMra2021838 . 232049825 .
  15. Yawalkar SJ . Milestones in the research and development of desferrioxamine . Nephrology, Dialysis, Transplantation . 8 . Suppl 1 . 40–42 . 1993 . 8389019 . 10.1093/ndt/8.supp1.40 .
  16. Lee HJ, Lee J, Lee SK, Lee SK, Kim EC . Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes . BMC Cancer . 7 . 176 . September 2007 . 17850672 . 2078595 . 10.1186/1471-2407-7-176 . free .
  17. Choi EY, Kim EC, Oh HM, Kim S, Lee HJ, Cho EY, Yoon KH, Kim EA, Han WC, Choi SC, Hwang JY, Park C, Oh BS, Kim Y, Kimm KC, Park KI, Chung HT, Jun CD . Iron chelator triggers inflammatory signals in human intestinal epithelial cells: involvement of p38 and extracellular signal-regulated kinase signaling pathways . Journal of Immunology . 172 . 11 . 7069–7077 . June 2004 . 15153529 . 10.4049/jimmunol.172.11.7069 . free .
  18. Web site: Public summary of opinion on orphan designation: Deferoxamine mesylate for the treatment of traumatic spinal cord injury . 3 October 2013 . Committee for Orphan Medicinal Products . European Medicines Agency . https://web.archive.org/web/20130717223511/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Forphans%2F2009%2F11%2Fhuman_orphan_000120.jsp&mid=WC0b01ac058001d12b . 2013-07-17 .
  19. Wu H, Wu T, Xu X, Wang J, Wang J . Iron toxicity in mice with collagenase-induced intracerebral hemorrhage . Journal of Cerebral Blood Flow and Metabolism . 31 . 5 . 1243–1250 . May 2011 . 21102602 . 3099628 . 10.1038/jcbfm.2010.209 .
  20. Ren H, Han R, Chen X, Liu X, Wan J, Wang L, Yang X, Wang J . Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update . Journal of Cerebral Blood Flow and Metabolism . 40 . 9 . 1752–1768 . September 2020 . 32423330 . 7446569 . 10.1177/0271678X20923551 .
  21. Ren H, Cao Y, Zhao Q, Li J, Zhou C, Liao L, Jia M, Zhao Q, Cai H, Han ZC, Yang R, Chen G, Zhao RC . Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions . Biochemical and Biophysical Research Communications . 347 . 1 . 12–21 . August 2006 . 16814746 . 10.1016/j.bbrc.2006.05.169 .
  22. Woo KJ, Lee TJ, Park JW, Kwon TK . Desferrioxamine, an iron chelator, enhances HIF-1alpha accumulation via cyclooxygenase-2 signaling pathway . Biochemical and Biophysical Research Communications . 343 . 1 . 8–14 . April 2006 . 16527254 . 10.1016/j.bbrc.2006.02.116 .
  23. Touma JG, Kelly C, Coblyn M, Jovanovic GN, Schilke K . Reversible Covalent Binding of Desferrioxamine B (DFOB) to Polystyrene Microspheres for the Chelation of Aqueous Iron Citrate . Industrial & Engineering Chemistry Research . 62 . 37 . 15109–15119 . 2023 . 10.1021/acs.iecr.3c00812.

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