Deferoxamine

Deferoxamine (Deferoxamine B) is an iron chelator (binds to Fe(III) and many other metal cations), is widely used to reduce iron accumulation and deposition in tissues. Deferoxamine upregulates HIF-1α levels with good antioxidant activity. Deferoxamine also shows anti-proliferative activity, can induce apoptosis and autophagy in cancer cells. Deferoxamine can be used in studies of diabetes, neurodegenerative diseases as well as anti-cancer and anti-COVID-19[1][2][3][4][5].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Research Areas >> Infection

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> PI3K/Akt/mTOR >> Akt

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Metabolic Enzyme/Protease >> HIF/HIF Prolyl-Hydroxylase

Research Areas >> Metabolic Disease

Research Areas >> Neurological Disease

Deferoxamine (1 mM; 16 h or 4 weeks) improves HIF-1α function under hypoxic and hyperglycemic conditions and decreases ROS in MEFs cells[1]. Deferoxamine (100 µM; 24 h) increases InsR expression and activity and also induces an increase in p-Akt/total Akt/PKB levels[2]. Deferoxamine (5, 10, 25, 50, 100 µM; 7 or 9 days) inhibits the proliferation of tumor-associated MSCs and bone marrow MSCs[3]. Deferoxamine (5, 10, 25, 50, 100 µM; 7 days) induces apoptosis of MSCs[3]. Deferoxamine (10 µM ; 3 days) influencs the expression of adhesion proteins on MSCs[3]. Deferoxamine (100 µM; 24 h) induces autophagy mediated by the level of HIF-1α in SH-SY5Y cells[4]. Western Blot Analysis[1] Cell Line: MEFs cells Concentration: 1 mM Incubation Time: 16 h (hypoxia condition); 4 weeks (hyperglycemic conditions) Result: Significantly attenuated the hyperglycemia-associated increase in ROS levels under hypoxic high glucose conditions. Notably increased normoxic HIF transactivation in MEFs under both high glucose and normal glucose conditions. Western Blot Analysis[2] Cell Line: HepG2 cells Concentration: 100 µM Incubation Time: 24 h Result: Showed a twofold increase of InsR mRNA levels in cells. Increased by twofold InsR binding activity at the half-maximal concentration of 1.1 nM. Cell Proliferation Assay[3] Cell Line: TAMSCs and BMMSCs (all isolated from Male C57BL/6J mice (8 week-old; EG-7 induced tumor model)) Concentration: 5, 10, 25, 50, 100 µM Incubation Time: 7 days (TAMSCs); 9 days (BMMSCs). Result: Inhibited the growth of TAMSCs and BMMSCs, and most cells are died at day 7 or 9 when exposed to 50 and 100 µM dose. Apoptosis Analysis[3] Cell Line: TAMSCs, BMMSCs Concentration: 5, 10, 25, 50, 100 µM Incubation Time: 7 days Result: Exhibited proapoptotic effect on TAMSCs and BMMSCs cells. Western Blot Analysis[3] Cell Line: TAMSCs, BMMSCs Concentration: 10 µM Incubation Time: 3 days Result: Remarkably decreased VCAM-1 expression in both TAMSCs and BMMSCs. Cell Autophagy Assay[4] Cell Line: SH-SY5Y cells Concentration: 100 µM Incubation Time: 24 h Result: Increased the ratio of LC3-II/I, an indicator of autophagy, which effects were blocked when autophagy-related gene Beclin 1 was suppressed by Beclin 1 siRNA transfection. Caused a time and dose-dependent increase of HIF-1a, accompanied by the induction of autophagy.

Deferoxamine (560.68 mg/per; drip-on; once daily for 21 days) enhances wound healing and increases neovascularization in aged or diabetic mice[1]. Deferoxamine (200 mg/kg; i.p.; daily for 2 weeks) results in HIF-1α stabilization and increases glucose uptake, hepatic InsR expression, and signaling in vivo[2]. Animal Model: Aged (21-month-old) and diabetic (12-week-old) C57BL/6J mice (excisional wound model)[1]. Dosage: 560.68 mg/per (10 uL of 1 mM) Administration: Drip-on; once daily for 21 days. Result: Displayed significantly accelerated healing and increased neovascularization in both aged and diabetic mice model. Animal Model: Male Sprague-Dawley rats (180-200 g)[2]. Dosage: 200 mg/kg Administration: Intraperitoneal injection; daily for 2 weeks. Result: Significantly increased hepatic HIF-1α protein levels, InsR protein levels, as well as Akt/PKB and activated Akt/PKB were significantly higher in the liver.

[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