Cell lines

RPE cells, 4 or 24h

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.

Reaction Conditions

0μM, 100μM, 260μM, or 500μM deferoxamine mesylate

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 models

Male Sprague-Dawley rats, 180-200g

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.

Dosage form

200mg/kg deferoxamine mesylate

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.

• Cell Death & Disease 13.6 (2022): 1-14. PMID: 35668064

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].

References:
[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.