Journal
ANTIOXIDANTS
Volume 10, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/antiox10081270
Keywords
iron; deferoxamine; antioxidant; ferroptosis; neuroprotection; outcome
Funding
- Fondo de Investigaciones Sanitarias-Instituto de Salud Carlos III [2007-006731-31]
- FEDER funds
- Agencia de Gestio d'Ajuts Universitaris i de Recerca [2019PROD00120, 2017 SGR 1520]
- INVICTUS PLUS [RD16/0019/0020]
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Iron has been studied as a potential target for preventing stroke-induced neurodegeneration, with iron chelator and antioxidant deferoxamine mesylate (DFO) showing potential therapeutic effects in ischemic stroke patients. DFO was found to be safe and effective in reducing iron saturation levels in blood transferrin. A trend towards improved clinical outcomes was observed in patients with moderate-severe ischemic stroke treated with DFO.
A role of iron as a target to prevent stroke-induced neurodegeneration has been recently revisited due to new evidence showing that ferroptosis inhibitors are protective in experimental ischemic stroke and might be therapeutic in other neurodegenerative brain pathologies. Ferroptosis is a new form of programmed cell death attributed to an overwhelming lipidic peroxidation due to excessive free iron and reactive oxygen species (ROS). This study aims to evaluate the safety and tolerability and to explore the therapeutic efficacy of the iron chelator and antioxidant deferoxamine mesylate (DFO) in ischemic stroke patients. Administration of placebo or a single DFO bolus followed by a 72 h continuous infusion of three escalating doses was initiated during the tPA infusion, and the impact on blood transferrin iron was determined. Primary endpoint was safety and tolerability, and secondary endpoint was good clinical outcome (clinicalTrials.gov NCT00777140). DFO was found safe as adverse effects were not different between placebo and DFO arms. DFO (40-60 mg/Kg/day) reduced the iron saturation of blood transferrin. A trend to efficacy was observed in patients with moderate-severe ischemic stroke (NIHSS > 7) treated with DFO 40-60 mg/Kg/day. A good outcome was observed at day 90 in 31% of placebo vs. 50-58% of the 40-60 mg/Kg/day DFO-treated patients.
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