去铁胺

去铁胺(去铁胺B)是一种铁螯合剂(与Fe(III)和许多其他金属阳离子结合),广泛用于减少组织中的铁积累和沉积。去铁胺通过良好的抗氧化活性上调HIF-1α水平。去铁胺还具有抗增殖活性,可诱导癌细胞凋亡和自噬。去铁胺可用于糖尿病、神经退行性疾病以及抗癌和抗新冠肺炎[1][2][3][4][5]的研究。

信号通路 >> 细胞凋亡 >> 细胞凋亡

研究领域 >> 癌症

研究领域 >> 感染

信号通路 >> 自噬 >> 自噬

信号通路 >> PI3K/Akt/mTOR 信号通路 >> AKT

研究领域 >> 炎症/免疫

信号通路 >> 代谢酶/蛋白酶 >> HIF/HIF脯氨酰-羟化酶

研究领域 >> 代谢疾病

研究领域 >> 神经疾病

去铁胺(1mM；16小时或4周)改善缺氧和高血糖条件下的HIF-1α功能,并减少MEFs细胞中的ROS[1]。去铁胺(100µM；24小时)增加InsR表达和活性,并诱导p-Akt/总Akt/PKB水平的增加[2]。去铁胺(5、10、25、50、100µM；7或9天)抑制肿瘤相关MSC和骨髓MSC的增殖[3]。去铁胺(5、10、25、50、100µM；7天)诱导骨髓间充质干细胞凋亡[3]。去铁胺(10µM；3天)影响MSC上粘附蛋白的表达[3]。去铁胺(100µM；24小时)诱导SH-SY5Y细胞中HIF-1α水平介导的自噬[4]。Western印迹分析[1]细胞系：MEFs细胞浓度：1mM,孵育时间：16h(缺氧条件)；4周(高血糖状态)结果：显著降低低氧高糖条件下高血糖相关的ROS水平升高。在高糖和正常葡萄糖条件下,MEF中的常氧HIF反式激活显著增加。Western Blot分析[2]细胞系：HepG2细胞浓度：100µM孵育时间：24小时结果：细胞内InsR mRNA水平增加两倍。在1.1nM的半最大浓度下增加了两倍的InsR结合活性。细胞增殖测定[3]细胞系：TAMSCs和BMMSCs(均从雄性C57BL/6J小鼠(8周龄；EG-7诱导的肿瘤模型)中分离)浓度：5、10、25、50、100µM,孵育时间：7天(TAMSCs)；9天(骨髓间充质干细胞)。结果：抑制TAMSC和BMMSC的生长,当暴露于50和100µM剂量时,大多数细胞在第7天或第9天死亡。凋亡分析[3]细胞系：TAMSCs,BMMSCs浓度：5、10、25、50、100µM孵育时间：7天结果：对TAMSCs和BMMSCs细胞显示促凋亡作用。Western Blot分析[3]细胞系：TAMSCs,BMMSCs浓度：10µM孵育时间：3天结果：TAMSC和BMMSCs中VCAM-1表达显著降低。细胞自噬测定[4]细胞系：SH-SY5Y细胞浓度：100µM孵育时间：24小时结果：增加了自噬指标LC3-II/I的比率,当自噬相关基因Beclin 1被Beclin 1siRNA转染抑制时,这种效应被阻断。导致HIF-1a的时间和剂量依赖性增加,同时诱导自噬。

去铁胺(560.68 mg/per；滴注；每日一次,持续21天)可促进老年或糖尿病小鼠的伤口愈合并增加新生血管[1]。去铁胺(200mg/kg；腹腔注射；每日2周)导致HIF-1α稳定,并增加体内葡萄糖摄取、肝脏InsR表达和信号[2]。动物模型：老年(21月龄)和糖尿病(12周龄)C57BL/6J小鼠(切除伤口模型)[1]。剂量：560.68毫克/每(10微升1mM)给药：滴注；每天一次,持续21天。结果：在老年和糖尿病小鼠模型中均显示出明显的加速愈合和增加的新生血管。动物模型：雄性Sprague-Dawley大鼠(180-200g)[2]。剂量：200mg/kg给药：腹腔注射；每日2周。结果：肝脏中显著升高的HIF-1α蛋白水平、InsR蛋白水平以及Akt/PKB和激活的Akt/PKB在肝脏中显著增高。

[1]. Duscher D, et al. Comparison of the Hydroxylase Inhibitor Dimethyloxalylglycine and the Iron Chelator Deferoxamine in Diabetic and Aged Wound Healing. Plast Reconstr Surg. 2017 Mar;139(3):695e-706e.

[2]. Dongiovanni P, et al. Iron depletion by deferoxamine up-regulates glucose uptake and insulin signaling in hepatoma cells and in rat liver. Am J Pathol. 2008 Mar;172(3):738-47.

[3]. Wang G, et al. In vitro assessment of deferoxamine on mesenchymal stromal cells from tumor and bone marrow. Environ Toxicol Pharmacol. 2017 Jan;49:58-64.

[4]. Wu Y, et al. Neuroprotection of deferoxamine on rotenone-induced injury via accumulation of HIF-1 alpha and induction of autophagy in SH-SY5Y cells. Neurochem Int. 2010 Oct;57(3):198-205.

[5]. Bellotti D, et al. Deferoxamine B: A Natural, Excellent and Versatile Metal Chelator. Molecules. 2021 May 28;26(11):3255.

MOLECULAR FORMULA :

C25-H48-N6-O8

MOLECULAR WEIGHT :

560.79

WISWESSER LINE NOTATION :

Z5NQV/2VM5NQV/ 21

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

12 gm/kg/17W-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - optic nerve neuropathy Sense Organs and Special Senses (Ear) - change in acuity

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Human

DOSE/DURATION :

37 gm/kg/2Y-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - optic nerve neuropathy

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

40 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - visual field changes Sense Organs and Special Senses (Eye) - hemorrhage

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

86 mg/kg/1H-C

TOXIC EFFECTS :

Blood - thrombocytopenia

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Multiple routes

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

440 mg/kg/6D-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - retinal changes (pigmentary depositions, retinitis, other)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

12240 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

329 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1340 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1680 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1450 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

250 mg/kg

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

52 gm/kg/52W-I

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - changes in lung weight Kidney, Ureter, Bladder - changes in bladder weight Endocrine - changes in adrenal weight

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

500 mg/kg/9D-I

TOXIC EFFECTS :

Nutritional and Gross Metabolic - changes in calcium Nutritional and Gross Metabolic - changes in iron Nutritional and Gross Metabolic - changes in metals, not otherwise specified

MUTATION DATA

TYPE OF TEST :

DNA inhibition

TEST SYSTEM :

Rodent - mouse Cells - not otherwise specified

DOSE/DURATION :

11 mg/L

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 35,1209,1985 *** REVIEWS *** TOXICOLOGY REVIEW CRTXB2 CRC Critical Reviews in Toxicology. (CRC Press, Inc., 2000 Corporate Blvd., NW, Boca Raton, FL 33431) V.1- 1971- Volume(issue)/page/year: 1(1),93,1971