Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke

Martínez-Alonso, Emma; Escobar-Peso, Alejandro; Ayuso, Maria I.; Gonzalo Gobernado, Rafael|||0000-0002-6357-105X; Chioua, Mourad; Montoya, Juan J.; Montaner, Joan|||0000-0003-4845-2279; Fernández, Israel|||0000-0002-0186-9774; Marco-Contelles, José; Alcázar, Alberto

Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke

Nitrones have a well-recognized capacity as spin-traps and are considered powerful free radical scavengers, which are two important issues in hypoxia-induced oxidative stress and cell death in brain ischemia. Consequently, nitrones have been proposed as therapeutic agents in acute ischemic stroke (A...

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Autores:	Martínez-Alonso, Emma, Escobar-Peso, Alejandro, Ayuso, Maria I., Gonzalo Gobernado, Rafael\|\|\|0000-0002-6357-105X, Chioua, Mourad, Montoya, Juan J., Montaner, Joan\|\|\|0000-0003-4845-2279, Fernández, Israel\|\|\|0000-0002-0186-9774, Marco-Contelles, José, Alcázar, Alberto
Tipo de recurso:	artículo
Fecha de publicación:	2020
País:	España
Institución:	Universitat Autònoma de Barcelona
Repositorio:	Dipòsit Digital de Documents de la UAB
Idioma:	inglés
OAI Identifier:	oai:ddd.uab.cat:252530
Acceso en línea:	https://ddd.uab.cat/record/252530 https://dx.doi.org/urn:doi:10.3390/antiox9040291
Access Level:	acceso abierto
Palabra clave:	Antioxidant Brain ischemia Hydroxyl radical Ischemic stroke Neuroprotection Nitrones Steroids Reactive oxygen species

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spelling	Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic StrokeMartínez-Alonso, EmmaEscobar-Peso, AlejandroAyuso, Maria I.Gonzalo Gobernado, Rafael\|\|\|0000-0002-6357-105XChioua, MouradMontoya, Juan J.Montaner, Joan\|\|\|0000-0003-4845-2279Fernández, Israel\|\|\|0000-0002-0186-9774Marco-Contelles, JoséAlcázar, AlbertoAntioxidantBrain ischemiaHydroxyl radicalIschemic strokeNeuroprotectionNitronesSteroidsReactive oxygen speciesNitrones have a well-recognized capacity as spin-traps and are considered powerful free radical scavengers, which are two important issues in hypoxia-induced oxidative stress and cell death in brain ischemia. Consequently, nitrones have been proposed as therapeutic agents in acute ischemic stroke (AIS). In this paper, we update the biological and pharmacological characterization of ISQ-201, a previously identified cholesteronitrone hybrid with antioxidant and neuroprotective activity. This study characterizes ISQ-201 as a neuroprotective agent against the hypoxia-induced ischemic injury. Transitory four-vessel occlusion and middle cerebral artery occlusion (tMCAO) were used to induce cerebral ischemia. Functional outcomes were determined using neurofunctional tests. Infarct area, neuronal death, and apoptosis induction were evaluated. In addition, ISQ-201 reactivity towards free radicals was studied in a theoretical model. ISQ-201 significantly decreased the ischemia-induced neuronal death and apoptosis, in a dose-dependent manner, showing its therapeutic effect when administered up until 6 h after post-ischemic reperfusion onset, effects that remained after 3 months from the ischemic episode. Furthermore, ISQ-201 significantly reduced infarct volume, leading to recovery of the motor function in the tMCAO model. Finally, the theoretical study confirmed the reactivity of ISQ-201 towards hydroxyl radicals. The results reported here prompted us to suggest ISQ-201 as a promising candidate for the treatment of AISUniversitat Autònoma de Barcelona 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/252530https://dx.doi.org/urn:doi:10.3390/antiox9040291reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00255Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RETICSRD16/0019/0006Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CTQ2016-78205-PMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 CTQ2016-81797-REDCInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 IFI18/00011open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2525302026-06-06T12:50:31Z
dc.title.none.fl_str_mv	Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke
title	Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke
spellingShingle	Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke Martínez-Alonso, Emma Antioxidant Brain ischemia Hydroxyl radical Ischemic stroke Neuroprotection Nitrones Steroids Reactive oxygen species
title_short	Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke
title_full	Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke
title_fullStr	Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke
title_full_unstemmed	Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke
title_sort	Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke
dc.creator.none.fl_str_mv	Martínez-Alonso, Emma Escobar-Peso, Alejandro Ayuso, Maria I. Gonzalo Gobernado, Rafael\|\|\|0000-0002-6357-105X Chioua, Mourad Montoya, Juan J. Montaner, Joan\|\|\|0000-0003-4845-2279 Fernández, Israel\|\|\|0000-0002-0186-9774 Marco-Contelles, José Alcázar, Alberto
author	Martínez-Alonso, Emma
author_facet	Martínez-Alonso, Emma Escobar-Peso, Alejandro Ayuso, Maria I. Gonzalo Gobernado, Rafael\|\|\|0000-0002-6357-105X Chioua, Mourad Montoya, Juan J. Montaner, Joan\|\|\|0000-0003-4845-2279 Fernández, Israel\|\|\|0000-0002-0186-9774 Marco-Contelles, José Alcázar, Alberto
author_role	author
author2	Escobar-Peso, Alejandro Ayuso, Maria I. Gonzalo Gobernado, Rafael\|\|\|0000-0002-6357-105X Chioua, Mourad Montoya, Juan J. Montaner, Joan\|\|\|0000-0003-4845-2279 Fernández, Israel\|\|\|0000-0002-0186-9774 Marco-Contelles, José Alcázar, Alberto
author2_role	author author author author author author author author author
dc.contributor.none.fl_str_mv	Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv	Antioxidant Brain ischemia Hydroxyl radical Ischemic stroke Neuroprotection Nitrones Steroids Reactive oxygen species
topic	Antioxidant Brain ischemia Hydroxyl radical Ischemic stroke Neuroprotection Nitrones Steroids Reactive oxygen species
description	Nitrones have a well-recognized capacity as spin-traps and are considered powerful free radical scavengers, which are two important issues in hypoxia-induced oxidative stress and cell death in brain ischemia. Consequently, nitrones have been proposed as therapeutic agents in acute ischemic stroke (AIS). In this paper, we update the biological and pharmacological characterization of ISQ-201, a previously identified cholesteronitrone hybrid with antioxidant and neuroprotective activity. This study characterizes ISQ-201 as a neuroprotective agent against the hypoxia-induced ischemic injury. Transitory four-vessel occlusion and middle cerebral artery occlusion (tMCAO) were used to induce cerebral ischemia. Functional outcomes were determined using neurofunctional tests. Infarct area, neuronal death, and apoptosis induction were evaluated. In addition, ISQ-201 reactivity towards free radicals was studied in a theoretical model. ISQ-201 significantly decreased the ischemia-induced neuronal death and apoptosis, in a dose-dependent manner, showing its therapeutic effect when administered up until 6 h after post-ischemic reperfusion onset, effects that remained after 3 months from the ischemic episode. Furthermore, ISQ-201 significantly reduced infarct volume, leading to recovery of the motor function in the tMCAO model. Finally, the theoretical study confirmed the reactivity of ISQ-201 towards hydroxyl radicals. The results reported here prompted us to suggest ISQ-201 as a promising candidate for the treatment of AIS
publishDate	2020
dc.date.none.fl_str_mv	2 2020-01-01 2020 2020-01-01
dc.type.none.fl_str_mv	Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://ddd.uab.cat/record/252530 https://dx.doi.org/urn:doi:10.3390/antiox9040291
url	https://ddd.uab.cat/record/252530 https://dx.doi.org/urn:doi:10.3390/antiox9040291
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.relation.none.fl_str_mv	Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00255 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RETICSRD16/0019/0006 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CTQ2016-78205-P Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CTQ2016-81797-REDC Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 IFI18/00011
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.source.none.fl_str_mv	reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona
instname_str	Universitat Autònoma de Barcelona
reponame_str	Dipòsit Digital de Documents de la UAB
collection	Dipòsit Digital de Documents de la UAB
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Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke

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