Article targeting pro-oxidant iron with deferoxamine as a treatment for ischemic stroke

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 o...

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Detalhes bibliográficos
Autores: Millán, Mónica, Gregorio-Rocasolano Barbany, Núria de|||0000-0001-5248-7525, Pérez de la Ossa, Natalia|||0000-0002-6063-211X, Reverté, Silvia|||0000-0002-2052-9978, Costa Pages, Joan, Giner, Pilar, Silva, Yolanda, Sobrino, Tomás|||0000-0002-9760-8690, Rodríguez-Yáñez, Manuel, Nombela, Florentino, Campos, Francisco|||0000-0001-8665-1039, Serena, Joaquín|||0000-0002-4478-7744, Vivancos, José, Martí-Sistac, Octavi, Cortés, Jordi|||0000-0002-3764-0795, Dávalos, Antoni|||0000-0003-2949-5679, Gasull Dalmau, Teresa|||0000-0002-9321-1741
Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:251152
Acesso em linha:https://ddd.uab.cat/record/251152
https://dx.doi.org/urn:doi:10.3390/antiox10081270
Access Level:acceso abierto
Palavra-chave:Iron
Deferoxamine
Antioxidant
Ferroptosis
Neuroprotection
Outcome
Descrição
Resumo: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.

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