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Repurposed Edaravone, Metformin, and Perampanel as a Potential Treatment for Hypoxia–Ischemia Encephalopathy: An In Vitro Study

Hypoxia–ischemia encephalopathy results from the interruption of oxygen delivery and blood flow to the brain. In the developing brain, it can lead to a brain injury, which is associated with high mortality rates and comorbidities. The hippocampus is one of the brain regions that may be affected by h...

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Autores principales: Silva, Daniela, Rocha, Ruben, Correia, Ana Salomé, Mota, Bárbara, Madeira, Maria Dulce, Vale, Nuno, Cardoso, Armando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775340/
https://www.ncbi.nlm.nih.gov/pubmed/36551799
http://dx.doi.org/10.3390/biomedicines10123043
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author Silva, Daniela
Rocha, Ruben
Correia, Ana Salomé
Mota, Bárbara
Madeira, Maria Dulce
Vale, Nuno
Cardoso, Armando
author_facet Silva, Daniela
Rocha, Ruben
Correia, Ana Salomé
Mota, Bárbara
Madeira, Maria Dulce
Vale, Nuno
Cardoso, Armando
author_sort Silva, Daniela
collection PubMed
description Hypoxia–ischemia encephalopathy results from the interruption of oxygen delivery and blood flow to the brain. In the developing brain, it can lead to a brain injury, which is associated with high mortality rates and comorbidities. The hippocampus is one of the brain regions that may be affected by hypoxia–ischemia with consequences on cognition. Unfortunately, clinically approved therapeutics are still scarce and limited. Therefore, in this study, we aimed to test three repurposed drugs with good pharmacological properties to evaluate if they can revert, or at least attenuate, the deleterious effects of hypoxia–ischemia in an in vitro model. Edaravone, perampanel, and metformin are used for the treatment of stroke and amyotrophic lateral sclerosis, some forms of epileptic status, and diabetes type 2, respectively. Through cell viability assays, morphology analysis, and detection of reactive oxygen species (ROS) production, in two different cell lines (HT-22 and SH-SY5Y), we found that edaravone and low concentrations of perampanel are able to attenuate cell damage induced by hypoxia and oxygen-glucose deprivation. Metformin did not attenuate hypoxic-induced events, at least in the initial phase. Among these repurposed drugs, edaravone emerged as the most efficient in the attenuation of events induced by hypoxia–ischemia, and the safest, since it did not exhibit significant cytotoxicity, even in high concentrations, and induced a decrease in ROS. Our results also reinforce the view that ROS and overexcitation play an important role in the pathophysiology of hypoxia–ischemia brain injury.
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spelling pubmed-97753402022-12-23 Repurposed Edaravone, Metformin, and Perampanel as a Potential Treatment for Hypoxia–Ischemia Encephalopathy: An In Vitro Study Silva, Daniela Rocha, Ruben Correia, Ana Salomé Mota, Bárbara Madeira, Maria Dulce Vale, Nuno Cardoso, Armando Biomedicines Article Hypoxia–ischemia encephalopathy results from the interruption of oxygen delivery and blood flow to the brain. In the developing brain, it can lead to a brain injury, which is associated with high mortality rates and comorbidities. The hippocampus is one of the brain regions that may be affected by hypoxia–ischemia with consequences on cognition. Unfortunately, clinically approved therapeutics are still scarce and limited. Therefore, in this study, we aimed to test three repurposed drugs with good pharmacological properties to evaluate if they can revert, or at least attenuate, the deleterious effects of hypoxia–ischemia in an in vitro model. Edaravone, perampanel, and metformin are used for the treatment of stroke and amyotrophic lateral sclerosis, some forms of epileptic status, and diabetes type 2, respectively. Through cell viability assays, morphology analysis, and detection of reactive oxygen species (ROS) production, in two different cell lines (HT-22 and SH-SY5Y), we found that edaravone and low concentrations of perampanel are able to attenuate cell damage induced by hypoxia and oxygen-glucose deprivation. Metformin did not attenuate hypoxic-induced events, at least in the initial phase. Among these repurposed drugs, edaravone emerged as the most efficient in the attenuation of events induced by hypoxia–ischemia, and the safest, since it did not exhibit significant cytotoxicity, even in high concentrations, and induced a decrease in ROS. Our results also reinforce the view that ROS and overexcitation play an important role in the pathophysiology of hypoxia–ischemia brain injury. MDPI 2022-11-25 /pmc/articles/PMC9775340/ /pubmed/36551799 http://dx.doi.org/10.3390/biomedicines10123043 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
Silva, Daniela
Rocha, Ruben
Correia, Ana Salomé
Mota, Bárbara
Madeira, Maria Dulce
Vale, Nuno
Cardoso, Armando
Repurposed Edaravone, Metformin, and Perampanel as a Potential Treatment for Hypoxia–Ischemia Encephalopathy: An In Vitro Study
title Repurposed Edaravone, Metformin, and Perampanel as a Potential Treatment for Hypoxia–Ischemia Encephalopathy: An In Vitro Study
title_full Repurposed Edaravone, Metformin, and Perampanel as a Potential Treatment for Hypoxia–Ischemia Encephalopathy: An In Vitro Study
title_fullStr Repurposed Edaravone, Metformin, and Perampanel as a Potential Treatment for Hypoxia–Ischemia Encephalopathy: An In Vitro Study
title_full_unstemmed Repurposed Edaravone, Metformin, and Perampanel as a Potential Treatment for Hypoxia–Ischemia Encephalopathy: An In Vitro Study
title_short Repurposed Edaravone, Metformin, and Perampanel as a Potential Treatment for Hypoxia–Ischemia Encephalopathy: An In Vitro Study
title_sort repurposed edaravone, metformin, and perampanel as a potential treatment for hypoxia–ischemia encephalopathy: an in vitro study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775340/
https://www.ncbi.nlm.nih.gov/pubmed/36551799
http://dx.doi.org/10.3390/biomedicines10123043
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