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Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial

  • Dades identificatives

    Identificador: imarina:9228502
    Autors:
    Millan, MonicaDeGregorio-Rocasolano, Nuriade la Ossa, Natalia PerezReverte, SilviaCosta, JoanGiner, PilarSilva, YolandaSobrino, TomasRodriguez-Yanez, ManuelNombela, FlorentinoCampos, FranciscoSerena, JoaquinVivancos, JoseMarti-Sistac, OctaviCortes, JordiDavalos, AntoniGasull, Teresa
    Resum:
    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.
  • Altres:

    Autor segons l'article: Millan, Monica; DeGregorio-Rocasolano, Nuria; de la Ossa, Natalia Perez; Reverte, Silvia; Costa, Joan; Giner, Pilar; Silva, Yolanda; Sobrino, Tomas; Rodriguez-Yanez, Manuel; Nombela, Florentino; Campos, Francisco; Serena, Joaquin; Vivancos, Jose; Marti-Sistac, Octavi; Cortes, Jordi; Davalos, Antoni; Gasull, Teresa;
    Departament: Infermeria
    Autor/s de la URV: REVERTÉ REVERTÉ, SANDRA / Reverté Villarroya, Silvia
    Paraules clau: Plasma iron Pharmacokinetics Oxidative stress Outcome Neuroprotection Model Iron Injury Focal cerebral-ischemia Ferroptosis Ferrioxamine Desferrioxamine Deferoxamine Brain-damage Antioxidant
    Resum: 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.
    Àrees temàtiques: Química Physiology Molecular biology Medicina ii Medicina i Interdisciplinar Food science & technology Food science Farmacia Engenharias ii Clinical biochemistry Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Chemistry, medicinal Cell biology Biotecnología Biodiversidade Biochemistry & molecular biology Biochemistry
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    Adreça de correu electrònic de l'autor: silvia.reverte@urv.cat
    Identificador de l'autor: 0000-0002-2052-9978
    Data d'alta del registre: 2024-09-28
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Antioxidants. 10 (8):
    Referència de l'ítem segons les normes APA: Millan, Monica; DeGregorio-Rocasolano, Nuria; de la Ossa, Natalia Perez; Reverte, Silvia; Costa, Joan; Giner, Pilar; Silva, Yolanda; Sobrino, Tomas; R (2021). Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial. Antioxidants, 10(8), -. DOI: 10.3390/antiox10081270
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2021
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Biochemistry,Biochemistry & Molecular Biology,Cell Biology,Chemistry, Medicinal,Clinical Biochemistry,Food Science,Food Science & Technology,Molecular Biology,Physiology
    Plasma iron
    Pharmacokinetics
    Oxidative stress
    Outcome
    Neuroprotection
    Model
    Iron
    Injury
    Focal cerebral-ischemia
    Ferroptosis
    Ferrioxamine
    Desferrioxamine
    Deferoxamine
    Brain-damage
    Antioxidant
    Química
    Physiology
    Molecular biology
    Medicina ii
    Medicina i
    Interdisciplinar
    Food science & technology
    Food science
    Farmacia
    Engenharias ii
    Clinical biochemistry
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Ciências agrárias i
    Ciência de alimentos
    Chemistry, medicinal
    Cell biology
    Biotecnología
    Biodiversidade
    Biochemistry & molecular biology
    Biochemistry
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