Author, as appears in the 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;
Department: Infermeria
URV's Author/s: Reverté Villarroya, Silvia
Keywords: Plasma iron Pharmacokinetics Oxidative stress Outcome Neuroprotection Model Iron Injury Focal cerebral-ischemia Ferroptosis Ferrioxamine Desferrioxamine Deferoxamine Brain-damage Antioxidant
Abstract: 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.
Thematic Areas: 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
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: silvia.reverte@urv.cat
Author identifier: 0000-0002-2052-9978
Record's date: 2023-08-05
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.mdpi.com/2076-3921/10/8/1270
Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Antioxidants. 10 (8):
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
Article's DOI: 10.3390/antiox10081270
Entity: Universitat Rovira i Virgili
Journal publication year: 2021
Publication Type: Journal Publications
Repositori URV