去铁胺
去铁胺 (英语:Deferoxamine ,简称DFOA,也可写为desferrioxamine),以Desferal品牌在市面销售,是一种可与铁和铝结合的药物,[1]专门用于治疗铁中毒、因多次输血或具有遗传性疾病而导致的血色沉着病以及个体因透析导致铝中毒。[1][2]此药物系透过肌肉注射、静脉注射或皮下注射方式给药。[1]
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![]() Skeletal formula and spacefill model of deferoxamine | |
临床资料 | |
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商品名 | Desferal |
其他名称 | desferrioxamine B、desferoxamine B、DFO-B, DFB及N'-[5-(Acetyl-hydroxy-amino)pentyl]-N-[5-[3-(5-aminopentyl-hydroxy-carbamoyl) propanoylamino]pentyl]-N-hydroxy-butane diamide |
AHFS/Drugs.com | Monograph |
给药途径 | |
ATC码 | |
药物动力学数据 | |
生物半衰期 | 6小时 |
识别信息 | |
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CAS号 | 70-51-9( ![]() |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.000.671 |
化学信息 | |
化学式 | C25H48N6O8 |
摩尔质量 | 560.69 g·mol−1 |
3D模型(JSmol) | |
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使用后常见的副作用有注射部位疼痛、腹泻、呕吐、发热、听力损失和眼睛问题。[1]可能会发生严重过敏反应,包括过敏性休克和低血压。[1]目前尚不清楚个体于怀孕期间使用是否会对胎儿,或是哺乳期间使用是否会对婴儿产生安全上的问题。[3]此药物是由革兰氏阳性菌毛链霉菌提炼出的的螯铁素制成。[4][5]
去铁胺于1968年在美国被批准用于医疗用途。[1]它已被列入世界卫生组织基本药物标准清单之中。[6]
医疗用途
编辑去铁胺用于治疗急性铁中毒(尤其是幼儿的[7])。此药物也常用于治疗血色沉着病(一种遗传性或后天性体内铁累积疾病)。后天性血色沉着常见于患有某些慢性贫血(例如地中海贫血和骨髓增生异常综合征)的患者,由于他们需要多次输血,而会大幅增加体内的铁含量。使用铁螯合药物(例如去铁胺)治疗,可降低依赖输血维生的镰刀型红血球疾病或β型地中海贫血患者的死亡率。[8]
针对慢性病症,通常透过每天间隔8-12小时的皮下注射给药。急性中毒后使用去铁胺可能会导致尿液呈现粉红色,此现象称为"桃红葡萄酒尿液(法语:vin rosé urine)"。除用于治疗铁中毒之外,还可用于治疗特定患者的铝中毒(体内铝过量)(但尚未获得美国食品药物管理局(FDA)批准用于此用途)。去铁胺也用于将阿霉素的心脏毒性副作用作最大限度降低,以及治疗铁蓝蛋白缺乏症。[9]去铁胺可能有效改善颅内出血患者的神经系统,但支持此适应症的有效性和安全性的证据很弱。[10]
不良影响
编辑目前尚不清楚个体于怀孕期间使用是否会对胎儿产生安全上的问题。[3]
罹患地中海贫血患者中属于thalassemia major类型的,长期使用此药物可能会增加其听力损失的风险。[13]
作用机制
编辑去铁胺是是由革兰氏阳性菌毛链霉菌所产生的螯铁素B,将其中三价铁离子部分移除而制成。发现此药物是汽巴精化(精细化工生产商)与瑞士苏黎世联邦理工学院和德国弗莱堡大学医院的科学家合作研究中无意中发现的结果。[15][4]去铁胺通过结合血液中的游离铁,也增强经由尿液消除。此药物可去除血色沉着症患者体内多余的铁,而减少对各种器官和组织(例如肝脏)造成损害。此外目前有有限的证据支持其能加速神经损伤的愈合。[16]去铁胺可调节特定细胞类型[17]发炎介质的表达[18]和释放。
研究
编辑目前有研究使用去铁胺于治疗脊髓损伤[19]和颅内出血。[20][21]它也用于研究诱导间充质干细胞中发生缺氧样环境(可激活一些与缺氧相关的信号通路,这些通路通常在缺氧环境下受激活后会发挥各种细胞保护作用)。[22][23]
由于去铁胺的末端氨基不会与金属螯合,因此被用于固定到各种工业和生物医学应用的表面和基材上(例如固定在过滤器上,用于去除水中的铁离子,固定在生物传感器的表面上,用于检测体液中的铁离子含量)。[24]
参见
编辑参考文献
编辑- ^ 1.0 1.1 1.2 1.3 1.4 1.5 Deferoxamine Mesylate. The American Society of Health-System Pharmacists. [2016-12-08]. (原始内容存档于2016-12-21).
- ^ World Health Organization. Stuart MC, Kouimtzi M, Hill SR , 编. WHO Model Formulary 2008. World Health Organization. 2009: 61–62. ISBN 9789241547659. hdl:10665/44053 .
- ^ 3.0 3.1 Deferoxamine (Desferal) Use During Pregnancy. www.drugs.com. [2016-12-13]. (原始内容存档于2016-12-21).
- ^ 4.0 4.1 Giardina PJ, Rivella S. Thalassemia Syndromes. Hoffman R, Benz Jr EJ, Silberstein LE, Heslop H, Weitz J, Anastasi J (编). Hematology: Diagnosis and Treatment 6th. Elsevier Health Sciences. 2012: 515. ISBN 978-1-4557-4041-3. (原始内容存档于2016-12-20) (英语).
- ^ Keberle H. The Biochemistry of Desferrioxamine and its Relation to Iron Metabolism. Annals of the New York Academy of Sciences. October 1964, 119 (2): 758–768. PMID 14219455. S2CID 37277528. doi:10.1111/j.1749-6632.1965.tb54077.x.
- ^ World Health Organization. World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. hdl:10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ^ Merlot AM, Kalinowski DS, Richardson DR. Novel chelators for cancer treatment: where are we now?. Antioxidants & Redox Signaling. March 2013, 18 (8): 973–1006. PMID 22424293. doi:10.1089/ars.2012.4540.
- ^ 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. July 2018, 93 (7): 943–952. PMID 29635754. doi:10.1002/ajh.25103 .
- ^ Miyajima H, Takahashi Y, Kamata T, Shimizu H, Sakai N, Gitlin JD. Use of desferrioxamine in the treatment of aceruloplasminemia. Annals of Neurology. March 1997, 41 (3): 404–407. PMID 9066364. S2CID 22425032. doi:10.1002/ana.410410318.
- ^ Zeng L, Tan L, Li H, Zhang Q, Li Y, Guo J. Deferoxamine therapy for intracerebral hemorrhage: A systematic review. PLOS ONE. 2018, 13 (3): e0193615. Bibcode:2018PLoSO..1393615Z. PMC 5863956 . PMID 29566000. doi:10.1371/journal.pone.0193615 .
- ^ Abobaker A. Can iron chelation as an adjunct treatment of COVID-19 improve the clinical outcome?. European Journal of Clinical Pharmacology. November 2020, 76 (11): 1619–1620. PMC 7325475 . PMID 32607779. doi:10.1007/s00228-020-02942-9.
- ^ 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. PMC 8108185 . doi:10.1080/20905068.2020.1870788.
- ^ Badfar G, Mansouri A, Shohani M, Karimi H, Khalighi Z, Rahmati S, et al. Hearing loss in Iranian thalassemia major patients treated with deferoxamine: A systematic review and meta-analysis. Caspian Journal of Internal Medicine. 2017, 8 (4): 239–249. PMC 5686301 . PMID 29201313. doi:10.22088/cjim.8.4.239.
- ^ Taher AT, Musallam KM, Cappellini MD. β-Thalassemias. The New England Journal of Medicine. February 2021, 384 (8): 727–743. PMID 33626255. S2CID 232049825. doi:10.1056/NEJMra2021838.
- ^ Yawalkar SJ. Milestones in the research and development of desferrioxamine. Nephrology, Dialysis, Transplantation. 1993, 8 (Suppl 1): 40–42. PMID 8389019. doi:10.1093/ndt/8.supp1.40.
- ^ Xu, Weilin; Guo, Zhen-Ni. Editorial: Ferroptosis in stroke, neurotrauma and neurodegeneration, volume II. Frontiers in Cellular Neuroscience. 2023-07-05 [2023-4-04-26]. doi:10.3389/fncel.2023.1238425. (原始内容存档于2024-04-26).
- ^ Choi EY, Kim EC, Oh HM, Kim S, Lee HJ, Cho EY, et al. Iron chelator triggers inflammatory signals in human intestinal epithelial cells: involvement of p38 and extracellular signal-regulated kinase signaling pathways. Journal of Immunology. June 2004, 172 (11): 7069–7077. PMID 15153529. doi:10.4049/jimmunol.172.11.7069 .
- ^ 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. September 2007, 7: 176. PMC 2078595 . PMID 17850672. doi:10.1186/1471-2407-7-176 .
- ^ Public summary of opinion on orphan designation: Deferoxamine mesylate for the treatment of traumatic spinal cord injury. Committee for Orphan Medicinal Products. European Medicines Agency. 2013-10-03. (原始内容存档于2013-07-17).
- ^ 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. May 2011, 31 (5): 1243–1250. PMC 3099628 . PMID 21102602. doi:10.1038/jcbfm.2010.209.
- ^ Ren H, Han R, Chen X, Liu X, Wan J, Wang L, et al. Potential therapeutic targets for intracerebral hemorrhage-associated inflammation: An update. Journal of Cerebral Blood Flow and Metabolism. September 2020, 40 (9): 1752–1768. PMC 7446569 . PMID 32423330. doi:10.1177/0271678X20923551.
- ^ Ren H, Cao Y, Zhao Q, Li J, Zhou C, Liao L, et al. Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions. Biochemical and Biophysical Research Communications. August 2006, 347 (1): 12–21. PMID 16814746. doi:10.1016/j.bbrc.2006.05.169.
- ^ 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. April 2006, 343 (1): 8–14. PMID 16527254. doi:10.1016/j.bbrc.2006.02.116.
- ^ Touma, J. G.; Kelly, C.; Coblyn, M.; Jovanovic, G. N.; Schilke, K. Reversible Covalent Binding of Desferrioxamine B (DFOB) to Polystyrene Microspheres for the Chelation of Aqueous Iron Citrate. Industrial & Engineering Chemistry Research. 2023, 62 (37): 15109–15119. doi:10.1021/acs.iecr.3c00812.