甲磺酸去铁胺

Deferoxamine mesylate是一种铁螯合剂,可将游离铁与稳定的复合物结合,防止其发生化学反应。

信号通路 >> 神经信号通路 >> β淀粉样蛋白

信号通路 >> 自噬 >> 自噬

信号通路 >> 自噬 >> 自噬

研究领域 >> 其他

在所有培养条件下,去铁胺处理显着增加HIF-1α结合,包括缺氧和高葡萄糖。去铁胺的机制是通过清除氧自由基来改善HIF-1α的生物学功能[1]。去铁胺(5μM)对肿瘤相关的基质细胞细胞增殖具有显着影响,并且细胞在暴露于50μM和100μM去铁胺后第7天死亡。去铁胺(5μM-100μM)抑制BMMSCs的增殖,并以剂量依赖性方式诱导MSC的凋亡。去铁胺影响MSCs粘附蛋白的表达[3]。去铁胺(30,60,120μM)在AdMSCs中以浓度依赖性方式显示HIF-1α的较低表达[4]。

去铁胺(100mg/kg,ip)降低蛛网膜下腔出血(SAH)大鼠的死亡率。去铁胺(100 mg/kg,ip)减弱皮层中Evan的蓝色外渗,改善紧密连接脱离并保持SAH后第3天在电子显微镜下检查的基膜的完整性。去铁胺可减轻SAH后BBB蛋白的降解,并显着降低皮质第3天的铁蛋白表达,并改善实验后的神经行为和认知缺陷[1]。从第7天开始,10μL的1mM去铁胺处理的伤口显示出显着加速的愈合,并且在糖尿病小鼠中愈合显着快于对照治疗的伤口。在老年小鼠中,去铁胺处理的伤口和二甲基肟基甘氨酸处理的伤口愈合明显快于对照处理的伤口[2]。在去铁胺(10mg/mL)处理的TG小鼠中,可溶性和不溶性Aβ40和Aβ42均降低。在去铁胺处理的小鼠中,pGSK3β和β-连环蛋白均显着增加约50％[5]。

将收获的鼠肿瘤和骨髓来源的MSC暴露于不同剂量的去铁胺。通过台盼蓝排除测定评估细胞活力。在参加实验之前，活细胞超过98％。将总共1.5×105个TAMSCs /孔或3×105个BMMSC /孔接种在6孔板中。然后在第二天将MSC暴露于5,10,25,50和100μM去铁胺。 7天后，计算TAMSCs的数量。为了评估去铁胺对原代骨髓MSC的细胞毒性，将2×106个骨髓细胞/孔接种在24孔板中。 9天后，计算存活细胞的数量。为了评估细胞周期，用碘化丙锭染色TAMSCs，并通过流式细胞术分析细胞周期分布。

将小鼠分为三个治疗组，每组17个：（1）给予IN去铁胺（TG-DFO）的TG小鼠，（2）给予IN磷酸盐缓冲盐水（TG-PBS）的TG小鼠，和（3）给予IN PBS的WT小鼠。 （WT-PBS）。在30周龄时，小鼠适应处理，然后在每周一，周三和周五鼻内治疗，从36周龄开始。给小鼠服药18周，直到54周的行为测试。在4周的行为期间继续给药以测量慢性和急性效应。行为后，给小鼠最后一次给药，24小时后对其进行安乐死并收集组织用于生化分析。这些包括通过ELISA和IHC测量的可溶性和不溶性淀粉样蛋白，用蛋白质印迹和氧化标记物定量蛋白质。

[1]. Li Y, et al. Effects of deferoxamine on blood-brain barrier disruption after subarachnoid hemorrhage. PLoS One. 2017 Mar 1;12(3):e0172784

[2]. 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

[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]. Wahl EA, et al. VEGF released by deferoxamine preconditioned mesenchymal stem cells seeded on collagen-GAG substrates enhances neovascularization. Sci Rep. 2016 Nov 10;6:36879

[5]. Fine JM, et al. Intranasal deferoxamine engages multiple pathways to decrease memory loss in the APP/PS1 model of amyloid accumulation. Neurosci Lett. 2015 Jan 1;584:362-7

3-甲基腺嘌呤 | 4-(4-氟苯基)-2-(4-甲基亚磺酰基苯基)-5-(4-吡啶基)-1H-咪唑 | U0126-EtOH | 阿卡地辛 | 布雷菲德菌素A | 坦螺旋霉素 | 白藜芦醇 | 褪黑素 | 姜黄素 | 盐霉素 | 2-乙基-3-甲基戊酰胺 | 槲皮素 | 雷公藤红素; 南蛇藤素 | 氯化血红素 | 4-氯-N-环己基-N-(苯基甲基)苯甲酰胺

MOLECULAR FORMULA :

C25-H48-N6-O8.C-H4-O3-S

MOLECULAR WEIGHT :

656.90

WISWESSER LINE NOTATION :

Z5NQV2VM5NQV2VM5NQV1 &WSQ1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

150 mg/kg/4D-I

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

REFERENCE :

BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 291,448,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

143 mg/kg/4D-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - visual field changes Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

REFERENCE :

BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857- Volume(issue)/page/year: 291,448,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

16 gm/kg/34W-I

TOXIC EFFECTS :

Cardiac - pericarditis Gastrointestinal - ulceration or bleeding from small intestine Blood - other changes

REFERENCE :

AJKDDP American Journal of Kidney Diseases. (Grune & Stratton, Inc., Journal Subscription Dept., POB 6280, Duluth, MN 55806) V.1- 1981- Volume(issue)/page/year: 10,71,1987

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

900 mg/kg/30W-I

TOXIC EFFECTS :

Brain and Coverings - other degenerative changes Cardiac - cardiomyopathy including infarction Lungs, Thorax, or Respiration - acute pulmonary edema

REFERENCE :

AJMEAZ American Journal of Medicine. (Technical Pub., 875 Third Ave., New York, NY 10022) V.1- 1946- Volume(issue)/page/year: 87,468,1989

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

17300 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,496,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

5500 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,496,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

330 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,496,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

15200 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,496,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1240 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 7,1181,1973

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1280 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 7,1181,1973

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

273 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,496,1982 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5340 No. of Facilities: 19 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 679 (estimated) No. of Female Employees: 350 (estimated)