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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/10/09 15:57:55」(JST)

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Deferoxamine (also known as desferrioxamine B, desferoxamine B, DFO-B, DFOA, DFB or desferal) is a bacterial siderophore produced by the actinobacteria Streptomyces pilosus. It has medical applications as a chelating agent used to remove excess iron from the body.^[1] The mesylate salt of DFO-B is commercially available.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.^[2]

Medical uses

Deferoxamine is used to treat acute iron poisoning, especially in small children. 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. Administration for chronic conditions is generally accomplished by subcutaneous injection (SQ infusion) 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 select patients. In America, the drug is not FDA-approved for this use.

Deferoxamine is also used to minimize Doxorubicin Cardiotoxic side effects.

Deferoxamine has also been used in the treatment of a patient with aceruloplasminemia.^[3]

Mechanism

Deferoxamine acts by binding free iron in the bloodstream and enhancing its elimination in the urine. By removing excess iron, the agent reduces the damage done to various organs and tissues, such as the liver. A recent study also shows that it speeds healing of nerve damage (and minimizes the extent of recent nerve trauma).^{[citation needed]} Deferoxamine may modulate expression^[4] and release of inflammatory mediators by specific cell types.^[5]

Research

Deferoxamine is being studied as a treatment for spinal cord injury.^[6]

References

^ Miller, Marvin J. (1989-11-01). "Syntheses and therapeutic potential of hydroxamic acid based siderophores and analogs". Chemical Reviews 89 (7): 1563–1579. doi:10.1021/cr00097a011.
^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.
^ Miyajima, H.; Takahashi, Y.; Kamata, T.; Shimizu, H.; Sakai, N.; Gitlin, J. D. : Use of desferrioxamine in the treatment of aceruloplasminemia. Ann. Neurol. 41: 404-407, 1997. PMID 9066364
^ 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. 2007 Sep 13;7:176. PMID 17850672
^ 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. J Immunol. 2004 Jun 1;172(11):7069-77. PMID 15153529
^ http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2009/11/human_orphan_000120.jsp&mid=WC0b01ac058001d12b

British National Formulary 55, March 2008; ISBN 978 085369 776 3 p. 32

UpToDate Contents

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1. サラセミアおよびその他の鉄過剰状態に対するキレート療法 chelation therapy for thalassemia and other iron overload states
2. 急性鉄中毒 acute iron poisoning
3. 慢性腎臓病におけるアルミニウム毒性 aluminum toxicity in chronic kidney disease
4. 鎌状赤血球症における赤血球輸血 red blood cell transfusion in sickle cell disease
5. ムコール症（接合真菌症） mucormycosis zygomycosis

English Journal

Therapeutic effect of deferoxamine on iron overload-induced inhibition of osteogenesis in a zebrafish model.

Chen B, Yan YL, Liu C, Bo L, Li GF, Wang H, Xu YJ.Author information Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, China.AbstractOsteoporosis results from an imbalance in bone remodeling, in which osteoclastic bone resorption exceeds osteoblastic bone formation. Iron has recently been recognized as an independent risk factor for osteoporosis. Reportedly, excess iron could promote osteoclast differentiation and bone resorption through the production of reactive oxygen species (ROS). We evaluated the effect of iron on osteoblast differentiation and bone formation in zebrafish and further investigated the potential benefits of deferoxamine (DFO), a powerful iron chelator, in iron-overloaded zebrafish. The zebrafish model of iron overload described in this study demonstrated an apparent inhibition of bone formation, accompanied by decreased expression of osteoblast-specific genes (runx2a, runx2b, osteocalcin, osteopontin, ALP, and collagen type I). The negative effect of iron on osteoblastic activity and bone formation could be attributed to increased ROS generation and oxidative stress. Most importantly, we revealed that DFO was capable of removing whole-body iron and attenuating oxidative stress in iron-overloaded larval zebrafish, which facilitated larval recovery from the reductions in bone formation and osteogenesis induced by iron overload.
Calcified tissue international.Calcif Tissue Int.2014 Mar;94(3):353-60. doi: 10.1007/s00223-013-9817-4. Epub 2014 Jan 12.
Osteoporosis results from an imbalance in bone remodeling, in which osteoclastic bone resorption exceeds osteoblastic bone formation. Iron has recently been recognized as an independent risk factor for osteoporosis. Reportedly, excess iron could promote osteoclast differentiation and bone resorption
PMID 24414856

Impact of antioxidants on the ability of phenolic phytochemicals to kill HCT116 colon cancer cells.

Murphy A, Testa K, Berkelhammer J, Hopkins S, Loo G.Author information Department of Nutrition, Cellular and Molecular Nutrition Research Laboratory, University of North Carolina at Greensboro , Greensboro, NC , USA.AbstractAbstract Certain phenolic phytochemicals can kill cancer cells. Possible interference from antioxidants is a concern, and this issue has not been studied appreciably. Therefore, the effect of ascorbate and N-acetylcysteine on the ability of epigallocatechin gallate (EGCG) and curcumin to kill HCT116 colon cancer cells was examined. EGCG and curcumin each caused DNA damage in the cells. The DNA-damaging ability of EGCG, but not curcumin, was hindered by either ascorbate or NAC, which was also shown in HT29 and SW480 colon cancer cells. Also, iron chelators (deferoxamine and 2,2'-dipyridyl) inhibited the ability of EGCG, but not curcumin, to cause damage to the DNA in HCT116 cells. Interestingly, curcumin, but not EGCG, increased the expression of growth arrest and DNA damage-inducible gene 153 and also heme oxygenase-1, and this stress gene upregulation by curcumin was antioxidant-insensitive. With prolonged incubation of HCT116 cells with either EGCG or curcumin, cell shrinkage, membrane blebbing, apoptotic bodies, and chromatin condensation/fragmentation were observed. These morphological changes were not apparent in EGCG-treated cells that had been pretreated with either ascorbate or NAC. However, the ascorbate and NAC pretreatments did not prevent the occurrence of the morphological changes in curcumin-treated cells. Thus, these findings suggest that ascorbate and NAC interfere with the ability of EGCG, but not curcumin, to kill HCT116 cells. This basic knowledge may help to better plan and optimize strategies for chemoprevention or chemotherapy.
Free radical research.Free Radic Res.2014 Mar;48(3):313-21. doi: 10.3109/10715762.2013.867958. Epub 2013 Dec 16.
Abstract Certain phenolic phytochemicals can kill cancer cells. Possible interference from antioxidants is a concern, and this issue has not been studied appreciably. Therefore, the effect of ascorbate and N-acetylcysteine on the ability of epigallocatechin gallate (EGCG) and curcumin to kill HCT116
PMID 24256565

Abnormal differentiation of dopaminergic neurons in zebrafish trpm7 mutant larvae impairs development of the motor pattern.

Decker AR1, McNeill MS2, Lambert AM3, Overton JD4, Chen YC5, Lorca RA6, Johnson NA7, Brockerhoff SE7, Mohapatra DP6, Macarthur H8, Panula P5, Masino MA3, Runnels LW4, Cornell RA9.Author information 1Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, United States.2Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA 52242, United States.3Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, United States.4UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, United States.5Neuroscience Center and Institute of Biomedicine/Anatomy, University of Helsinki, Helsinki, Finland.6Department of Pharmacology, University of Iowa, Iowa City, IA 52245, United States.7Department of Biochemistry, University of Washington, Seattle, WA 98195, United States.8Department of Pharmacological and Physiological Science, St. Louis University, St. Louis, MO 63104, United States.9Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, United States; Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA 52242, United States. Electronic address: robert-cornell@uiowa.edu.AbstractTransient receptor potential, melastatin-like 7 (Trpm7) is a combined ion channel and kinase implicated in the differentiation or function of many cell types. Early lethality in mice and frogs depleted of the corresponding gene impedes investigation of the functions of this protein particularly during later stages of development. By contrast, zebrafish trpm7 mutant larvae undergo early morphogenesis normally and thus do not have this limitation. The mutant larvae are characterized by multiple defects including melanocyte cell death, transient paralysis, and an ion imbalance that leads to the development of kidney stones. Here we report a requirement for Trpm7 in differentiation or function of dopaminergic neurons in vivo. First, trpm7 mutant larvae are hypomotile and fail to make a dopamine-dependent developmental transition in swim-bout length. Both of these deficits are partially rescued by the application of levodopa or dopamine. Second, histological analysis reveals that in trpm7 mutants a significant fraction of dopaminergic neurons lack expression of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Third, trpm7 mutants are unusually sensitive to the neurotoxin 1-methyl-4-phenylpyridinium, an oxidative stressor, and their motility is partially rescued by application of the iron chelator deferoxamine, an anti-oxidant. Finally, in SH-SY5Y cells, which model aspects of human dopaminergic neurons, forced expression of a channel-dead variant of TRPM7 causes cell death. In summary, a forward genetic screen in zebrafish has revealed that both melanocytes and dopaminergic neurons depend on the ion channel Trpm7. The mechanistic underpinning of this dependence requires further investigation.
Developmental biology.Dev Biol.2014 Feb 15;386(2):428-39. doi: 10.1016/j.ydbio.2013.11.015. Epub 2013 Nov 27.
Transient receptor potential, melastatin-like 7 (Trpm7) is a combined ion channel and kinase implicated in the differentiation or function of many cell types. Early lethality in mice and frogs depleted of the corresponding gene impedes investigation of the functions of this protein particularly duri
PMID 24291744

Japanese Journal

フッ素によるアルミニウムに依存した Na, K-ATPase 活性の抑制

石川一郎,出山義昭,吉村善隆,鈴木邦明
北海道歯学雑誌 31(2), 44-51, 2010-12-15
… NaFとKFはNa,K-ATPase活性を濃度に依存して抑制し，50%阻害濃度(Ki0.5)は約1.4mMであった.0.25mMF存在下での活性抑制は約10%であり，2.5mMではほぼ完全に抑制された.FによるKi0.5はアルミニウム(A1)存在下でA1の濃度に依存して減少し，A1のキレーターであるdeferoxamine存在下では増加した. …
NAID 10028208506

Iron chelation therapy in the management of thalassemia : the Asian perspectives

VIPRAKASIT Vip,LEE-LEE Chan,CHONG Quah Thuan,LIN Kai-Hsin,KHUHAPINANT Archrob
International journal of hematology 90(4), 435-445, 2009-11-15
NAID 10026109273

Related Pictures

★リンクテーブル★

リンク元	「デフェロキサミン」「desferrioxamine」
拡張検索	「deferoxamine mesilate」「deferoxamine mesylate」

「デフェロキサミン」

Deferoxamine
	IUPAC name N'-{5-[Acetyl(hydroxy)amino]pentyl}-N-[5-({4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanoyl}amino)pentyl]-N-hydroxysuccinamide
	Other names N'-[5-(Acetyl-hydroxy-amino)pentyl]-N-[5-[3-(5-aminopentyl-hydroxy-carbamoyl) propanoylamino]pentyl]-N-hydroxy-butane diamide
Identifiers
CAS number	70-51-9
PubChem	2973
ChemSpider	2867
UNII	J06Y7MXW4D
DrugBank	DB00746
KEGG	D03670
ChEBI	CHEBI:4356
ChEMBL	CHEMBL556
ATC code	V03AC01
Beilstein Reference	2514118
Jmol-3D images	Image 1; Image 2
	SMILES Cc(:[o]):n(:[oH])CCCCC[nH]:c(:[o])CCc(:[o]):n(:[oH])CCCCC[nH]:c(:[o])CCc(:[o]):n(:[oH])CCCCCN CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN ;
	InChI InChI=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) ; Key: UBQYURCVBFRUQT-UHFFFAOYSA-N ;
Properties
Molecular formula	C25H48N6O8
Molar mass	560.68 g mol−1
log P	−0.614
Acidity (pKa)	9.079
Basicity (pKb)	4.918
Pharmacology
Routes of; administration	Intramuscular; Intraperitoneal; Intravenous; Oral; Subcutaneous;
Elimination; half-life	6 hours
Related compounds
Related alkanamides	Stearamidopropyl dimethylamine
	Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
	Infobox references