deferoxamine

Deferoxamine is used to treat acute iron poisoning, especially in small children.{{cite journal | vauthors = Merlot AM, Kalinowski DS, Richardson DR | title = Novel chelators for cancer treatment: where are we now? | journal = Antioxidants & Redox Signaling | volume = 18 | issue = 8 | pages = 973–1006 | date = March 2013 | pmid = 22424293 | doi = 10.1089/ars.2012.4540 }} 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.{{cite journal | vauthors = Ballas SK, Zeidan AM, Duong VH, DeVeaux M, Heeney MM | title = The effect of iron chelation therapy on overall survival in sickle cell disease and β-thalassemia: A systematic review | journal = American Journal of Hematology | volume = 93 | issue = 7 | pages = 943–952 | date = July 2018 | pmid = 29635754 | doi = 10.1002/ajh.25103 | doi-access = free }}

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.{{cite journal | vauthors = Miyajima H, Takahashi Y, Kamata T, Shimizu H, Sakai N, Gitlin JD | title = Use of desferrioxamine in the treatment of aceruloplasminemia | journal = Annals of Neurology | volume = 41 | issue = 3 | pages = 404–407 | date = March 1997 | pmid = 9066364 | doi = 10.1002/ana.410410318 | s2cid = 22425032 }} 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.{{cite journal | vauthors = Zeng L, Tan L, Li H, Zhang Q, Li Y, Guo J | title = Deferoxamine therapy for intracerebral hemorrhage: A systematic review | journal = PLOS ONE | volume = 13 | issue = 3 | pages = e0193615 | date = 2018 | pmid = 29566000 | pmc = 5863956 | doi = 10.1371/journal.pone.0193615 | doi-access = free | bibcode = 2018PLoSO..1393615Z }}

Some published manuscripts suggesting the use of deferoxamine for patients diagnosed with COVID-19 because of the high level of ferritin among them.{{cite journal | vauthors = Abobaker A | title = Can iron chelation as an adjunct treatment of COVID-19 improve the clinical outcome? | journal = European Journal of Clinical Pharmacology | volume = 76 | issue = 11 | pages = 1619–1620 | date = November 2020 | pmid = 32607779 | pmc = 7325475 | doi = 10.1007/s00228-020-02942-9 | url = }}{{cite journal | vauthors = Alkattan A, Alabdulkareem K, Kamel A, Abdelseed H, Almutairi Y, Alsalameen E | title = Correlation between Micronutrient plasma concentration and disease severity in COVID-19 patients. | journal = Alexandria Journal of Medicine | date = January 2021 | volume = 57 | issue = 1 | pages = 21–27 | doi = 10.1080/20905068.2020.1870788 | pmc = 8108185 }}

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

Chronic use of deferoxamine may increase the risk of hearing loss in patients with thalassemia major.{{cite journal | vauthors = Badfar G, Mansouri A, Shohani M, Karimi H, Khalighi Z, Rahmati S, Delpisheh A, Veisani Y, Soleymani A, Azami M | title = Hearing loss in Iranian thalassemia major patients treated with deferoxamine: A systematic review and meta-analysis | journal = Caspian Journal of Internal Medicine | volume = 8 | issue = 4 | pages = 239–249 | date = 2017 | pmid = 29201313 | pmc = 5686301 | doi = 10.22088/cjim.8.4.239 }}

Chronic use of deferoxamine may cause ocular symptoms, growth retardation, local reactions and allergy.{{cite journal | vauthors = Taher AT, Musallam KM, Cappellini MD | title = β-Thalassemias | journal = The New England Journal of Medicine | volume = 384 | issue = 8 | pages = 727–743 | date = February 2021 | pmid = 33626255 | doi = 10.1056/NEJMra2021838 | s2cid = 232049825 }}

Deferoxamine is produced by removal of the trivalent iron moiety from ferrioxamine B, an iron-bearing siderophore 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{{cite journal | vauthors = Yawalkar SJ | title = Milestones in the research and development of desferrioxamine | journal = Nephrology, Dialysis, Transplantation | volume = 8 | issue = Suppl 1 | pages = 40–42 | date = 1993 | pmid = 8389019 | doi = 10.1093/ndt/8.supp1.40 }} 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).{{Citation needed|reason=A citation is needed for the claim that a recent study has shown DFO to speed nerve regeneration|date=August 2013}} Deferoxamine may modulate expression{{cite journal | vauthors = Lee HJ, Lee J, Lee SK, Lee SK, Kim EC | title = Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes | journal = BMC Cancer | volume = 7 | pages = 176 | date = September 2007 | pmid = 17850672 | pmc = 2078595 | doi = 10.1186/1471-2407-7-176 | doi-access = free }} and release of inflammatory mediators by specific cell types.{{cite journal | vauthors = 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 | title = Iron chelator triggers inflammatory signals in human intestinal epithelial cells: involvement of p38 and extracellular signal-regulated kinase signaling pathways | journal = Journal of Immunology | volume = 172 | issue = 11 | pages = 7069–7077 | date = June 2004 | pmid = 15153529 | doi = 10.4049/jimmunol.172.11.7069 | doi-access = free }}

Deferoxamine is being studied as a treatment for spinal cord injury{{cite web | title = Public summary of opinion on orphan designation: Deferoxamine mesylate for the treatment of traumatic spinal cord injury | date = 3 October 2013 | work = Committee for Orphan Medicinal Products | publisher = European Medicines Agency | url = http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2009/11/human_orphan_000120.jsp&mid=WC0b01ac058001d12b | archive-url = 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 | archive-date=2013-07-17 }} and intracerebral hemorrhage.{{cite journal | vauthors = Wu H, Wu T, Xu X, Wang J, Wang J | title = Iron toxicity in mice with collagenase-induced intracerebral hemorrhage | journal = Journal of Cerebral Blood Flow and Metabolism | volume = 31 | issue = 5 | pages = 1243–1250 | date = May 2011 | pmid = 21102602 | pmc = 3099628 | doi = 10.1038/jcbfm.2010.209 }}{{cite journal | vauthors = Ren H, Han R, Chen X, Liu X, Wan J, Wang L, Yang X, Wang J | title = Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update | journal = Journal of Cerebral Blood Flow and Metabolism | volume = 40 | issue = 9 | pages = 1752–1768 | date = September 2020 | pmid = 32423330 | pmc = 7446569 | doi = 10.1177/0271678X20923551 }} It is also used to induce hypoxia-like environment in mesenchymal stem cells.{{cite journal | vauthors = 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 | title = Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions | journal = Biochemical and Biophysical Research Communications | volume = 347 | issue = 1 | pages = 12–21 | date = August 2006 | pmid = 16814746 | doi = 10.1016/j.bbrc.2006.05.169 }}{{cite journal | vauthors = Woo KJ, Lee TJ, Park JW, Kwon TK | title = Desferrioxamine, an iron chelator, enhances HIF-1alpha accumulation via cyclooxygenase-2 signaling pathway | journal = Biochemical and Biophysical Research Communications | volume = 343 | issue = 1 | pages = 8–14 | date = April 2006 | pmid = 16527254 | doi = 10.1016/j.bbrc.2006.02.116 }}

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.{{cite journal | vauthors = Touma JG, Kelly C, Coblyn M, Jovanovic GN, Schilke K | title = Reversible Covalent Binding of Desferrioxamine B (DFOB) to Polystyrene Microspheres for the Chelation of Aqueous Iron Citrate | journal = Industrial & Engineering Chemistry Research | volume = 62 | issue = 37 | pages = 15109–15119 | date = 2023 | doi = 10.1021/acs.iecr.3c00812}}

• Chelation therapy

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Category:Siderophores

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