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Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke

Nitrones are encouraging drug candidates for the treatment of oxidative stress-driven diseases such as acute ischemic stroke (AIS). In a previous study, we found a promising quinolylnitrone, QN23, which exerted a neuroprotective effect in neuronal cell cultures subjected to oxygen–glucose deprivatio...

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Autores principales: Martínez-Alonso, Emma, Escobar-Peso, Alejandro, Aliena-Valero, Alicia, Torregrosa, Germán, Chioua, Mourad, Fernández-Serra, Rocío, González-Nieto, Daniel, Ouahid, Youness, Salom, Juan B., Masjuan, Jaime, Marco-Contelles, José, Alcázar, Alberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220178/
https://www.ncbi.nlm.nih.gov/pubmed/35740081
http://dx.doi.org/10.3390/antiox11061186
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author Martínez-Alonso, Emma
Escobar-Peso, Alejandro
Aliena-Valero, Alicia
Torregrosa, Germán
Chioua, Mourad
Fernández-Serra, Rocío
González-Nieto, Daniel
Ouahid, Youness
Salom, Juan B.
Masjuan, Jaime
Marco-Contelles, José
Alcázar, Alberto
author_facet Martínez-Alonso, Emma
Escobar-Peso, Alejandro
Aliena-Valero, Alicia
Torregrosa, Germán
Chioua, Mourad
Fernández-Serra, Rocío
González-Nieto, Daniel
Ouahid, Youness
Salom, Juan B.
Masjuan, Jaime
Marco-Contelles, José
Alcázar, Alberto
author_sort Martínez-Alonso, Emma
collection PubMed
description Nitrones are encouraging drug candidates for the treatment of oxidative stress-driven diseases such as acute ischemic stroke (AIS). In a previous study, we found a promising quinolylnitrone, QN23, which exerted a neuroprotective effect in neuronal cell cultures subjected to oxygen–glucose deprivation and in experimental models of cerebral ischemia. In this paper, we update the biological and pharmacological characterization of QN23. We describe the suitability of intravenous administration of QN23 to induce neuroprotection in transitory four-vessel occlusion (4VO) and middle cerebral artery occlusion (tMCAO) experimental models of brain ischemia by assessing neuronal death, apoptosis induction, and infarct area, as well as neurofunctional outcomes. QN23 significantly decreased the neuronal death and apoptosis induced by the ischemic episode in a dose-dependent manner and showed a therapeutic effect when administered up to 3 h after post-ischemic reperfusion onset, effects that remained 11 weeks after the ischemic episode. In addition, QN23 significantly reduced infarct volume, thus recovering the motor function in a tMCAO model. Remarkably, we assessed the antioxidant activity of QN23 in vivo using dihydroethidium as a molecular probe for radical species. Finally, we describe QN23 pharmacokinetic parameters. All these results pointing to QN23 as an interesting and promising preclinical candidate for the treatment of AIS.
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spelling pubmed-92201782022-06-24 Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke Martínez-Alonso, Emma Escobar-Peso, Alejandro Aliena-Valero, Alicia Torregrosa, Germán Chioua, Mourad Fernández-Serra, Rocío González-Nieto, Daniel Ouahid, Youness Salom, Juan B. Masjuan, Jaime Marco-Contelles, José Alcázar, Alberto Antioxidants (Basel) Article Nitrones are encouraging drug candidates for the treatment of oxidative stress-driven diseases such as acute ischemic stroke (AIS). In a previous study, we found a promising quinolylnitrone, QN23, which exerted a neuroprotective effect in neuronal cell cultures subjected to oxygen–glucose deprivation and in experimental models of cerebral ischemia. In this paper, we update the biological and pharmacological characterization of QN23. We describe the suitability of intravenous administration of QN23 to induce neuroprotection in transitory four-vessel occlusion (4VO) and middle cerebral artery occlusion (tMCAO) experimental models of brain ischemia by assessing neuronal death, apoptosis induction, and infarct area, as well as neurofunctional outcomes. QN23 significantly decreased the neuronal death and apoptosis induced by the ischemic episode in a dose-dependent manner and showed a therapeutic effect when administered up to 3 h after post-ischemic reperfusion onset, effects that remained 11 weeks after the ischemic episode. In addition, QN23 significantly reduced infarct volume, thus recovering the motor function in a tMCAO model. Remarkably, we assessed the antioxidant activity of QN23 in vivo using dihydroethidium as a molecular probe for radical species. Finally, we describe QN23 pharmacokinetic parameters. All these results pointing to QN23 as an interesting and promising preclinical candidate for the treatment of AIS. MDPI 2022-06-16 /pmc/articles/PMC9220178/ /pubmed/35740081 http://dx.doi.org/10.3390/antiox11061186 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Martínez-Alonso, Emma
Escobar-Peso, Alejandro
Aliena-Valero, Alicia
Torregrosa, Germán
Chioua, Mourad
Fernández-Serra, Rocío
González-Nieto, Daniel
Ouahid, Youness
Salom, Juan B.
Masjuan, Jaime
Marco-Contelles, José
Alcázar, Alberto
Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke
title Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke
title_full Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke
title_fullStr Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke
title_full_unstemmed Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke
title_short Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke
title_sort preclinical characterization of antioxidant quinolyl nitrone qn23 as a new candidate for the treatment of ischemic stroke
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220178/
https://www.ncbi.nlm.nih.gov/pubmed/35740081
http://dx.doi.org/10.3390/antiox11061186
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