Deferoxamine mesylate is a drug that chelates iron by forming a stable complex that prevents the iron from entering into further chemical reactions, and is used for the treatment of chronic iron overload in patients with transfusion-dependent anemias[1,2].
Deferoxamine mesylate (260μM) is directly toxic on RPE cells, its toxicity depending on p38[1]. Deferoxamine mesylate administration resulted in reduced cytotoxicity and ROS generation by Fe(Salen) in Rabbit squamous cell carcinoma (VX2) cells, human glioblastoma malignant glioma cells (YKG)OVK18, and human ovarian carcinoma cells[3]. Deferoxamine mesylate (30μM) significantly inhibits the growth of human hepatocellular carcinoma and hepatoblastoma cell lines[4].
Deferoxamine mesylate enhances urinary iron elimination and decreases hepatic iron accumulation after blood transfusion in foals[2]. Deferoxamine mesylate (25mg/kg, intravenous injection) reduced the onset of Fe (Salen) (25mg/kg)-induced acute liver and renal dysfunction. Deferoxamine mesylate (300mg/kg) improves survival rate after systematic injection of a fatal dose of Fe (Salen) (200mg/kg) in Male ICR[3]. Use of deferoxamine mesylate in bone defects promotes vascularization and osteogenesis in the defect area, and maintains the protein activity of HIF-1α temporarily[5]. Deferoxamine mesylate can ameliorate tissue ischemia-reperfusion injury. Deferoxamine mesylate preconditioning protected pancreatic tissue in orthotopic liver autotransplantation in rats[6].
参考文献:
[1] Klettner A, Koinzer S, et al. Deferoxamine mesylate is toxic for retinal pigment epithelium cells in vitro, and its toxicity is mediated by p38. Cutan Ocul Toxicol. 2010;29(2):122-129.
[2] Elfenbein JR, Giguère S, et al. The effects of deferoxamine mesylate on iron elimination after blood transfusion in neonatal foals. J Vet Intern Med. 2010;24(6):1475-1482.
[3] Umemura M, Kim JH, et al. The iron chelating agent, deferoxamine detoxifies Fe(Salen)-induced cytotoxicity. J Pharmacol Sci. 2017;134(4):203-210.
[4] Tabor E, Kim CM. Inhibition of human hepatocellular carcinoma and hepatoblastoma cell lines by deferoxamine. J Med Virol. 1991;34(1):45-50.
[5]DU WY, Yang JW, et al. [Early constant observation of the effect of deferoxamine mesylate on improvement of vascularized bone regeneration in SD rat skull critical size defect model]. Beijing Da Xue Xue Bao Yi Xue Ban. 2021 Dec 18;53(6):1171-1177. Chinese.
[6]Li Y, Zhang PJ, et al. Protective effects of deferoxamine mesylate preconditioning on pancreatic tissue in orthotopic liver autotransplantation in rats. Transplant Proc. 2011;43(5):1450-1455.
Deferoxamine mesylate 是一种通过形成稳定的复合物来螯合铁的药物，该复合物可防止铁进入进一步的化学反应，并用于治疗输血依赖性贫血患者的慢性铁过载[1, 2].
Deferoxamine mesylate (260μM) 对 RPE 细胞有直接毒性，其毒性取决于 p38[1]。施用甲磺酸去铁胺可降低兔鳞状细胞癌 (VX2) 细胞、人胶质母细胞瘤恶性胶质瘤细胞 (YKG)OVK18 和人卵巢癌细胞中 Fe(Salen) 的细胞毒性和 ROS 生成[3] . Deferoxamine mesylate (30μM)显着抑制人肝细胞癌和肝母细胞瘤细胞系的生长[4]。
甲磺酸去铁胺增强马驹输血后尿液铁的消除并减少肝脏铁的积累[2]。 Deferoxamine mesylate (25mg/kg, 静脉注射)减少了Fe (Salen) (25mg/kg)诱导的急性肝肾功能障碍的发生。甲磺酸去铁胺 (300mg/kg) 在男性 ICR[3] 中系统注射致命剂量的 Fe (Salen) (200mg/kg) 后提高了存活率。甲磺酸去铁胺在骨缺损中的应用促进了缺损区域的血管形成和成骨，并暂时维持了HIF-1α的蛋白活性[5]。 Deferoxamine mesylate 可以改善组织缺血再灌注损伤。甲磺酸去铁胺预处理对大鼠原位自体肝移植胰腺组织的保护作用[6].
| Cell experiment [1]: | |
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Cell lines |
RPE cells, 4 or 24h |
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Preparation Method |
Subconfluent RPE cells were stimulated for 4 hours or 24 hours with 0μM, 100μM, 260μM, or 500μM of deferoxamine mesylate suspended in sterile distilled water. |
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Reaction Conditions |
0μM, 100μM, 260μM, or 500μM deferoxamine mesylate |
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Applications |
Deferoxamine mesylate induces significant cell death compared with untreated controls in the RPE cells when treated for 4 hours or 24 hours with 260μM and 500μM, but not when treated with 100μM, of deferoxamine. |
| Animal experiment [2]: | |
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Animal models |
Male Sprague-Dawley rats, 180-200g |
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Preparation Method |
Rats were either iron depleted by daily injections of 200mg/kg deferoxamine mesylate (Novartis)37 or submitted to injections of solvent (0.9% saline), for 2 weeks. |
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Dosage form |
200mg/kg deferoxamine mesylate |
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Applications |
Iron depletion by deferoxamine mesylate affects glucose metabolism inducing glucose uptake and utilization and increasing InsR binding activity and signaling, and that the mechanism is associated with HIF-1 stabilization and requires the presence of HIF-1/ARNT. |
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参考文献: [1]. Klettner A, Koinzer S, et al. Deferoxamine mesylate is toxic for retinal pigment epithelium cells in vitro, and its toxicity is mediated by p38. Cutan Ocul Toxicol. 2010;29(2):122-129. [2]. Dongiovanni P, Valenti L, et al. Iron depletion by deferoxamine up-regulates glucose uptake and insulin signaling in hepatoma cells and in rat liver. Am J Pathol. 2008;172(3):738-747. |
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