Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury

Autores
Toro Urrego, Nicolas; Luaces, Juan Pablo; Bordet, Sofía; Otero-losada, Matilde Estela; Capani, Francisco
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background. Hypoxic-ischemic brain injury is one primary cause of long-term neurologicaldisability, morbidity, and death worldwide. The decrease in blood flow and oxygen concentration leads toinsufficient nutrient supply to the brain, energy depletion, increased free radical generation, and mitochondrialdysfunction. Perinatal asphyxia — the oxygen supply suspension near birth-time — causes hypoxic-ischemicbrain injury and is a major risk factor for neurodevelopmental damage. In pathological scenarios, raloxifene, aselective estrogen receptor modulator, has shown neuroprotective effects. Purpose. To examine whetherraloxifene showed neuroprotection in an oxygen-glucose deprivation/reoxygenation astrocyte cell model.Methods. T98G cells in culture were treated with a glucose-free DMEM medium and incubated at 37ºC in ahypoxia chamber with 1% O2 for 3, 6, 12, and 24 hours. Cultures were supplemented with raloxifene 1, 10, and100 nM during both glucose and oxygen deprivation and reoxygenation periods. Results. Raloxifene 100 nMand 10 nM improved cell survival — 65.34% and 70.56% — respectively compared to the control cell groups.Mitochondrial membrane potential was preserved by 58.9% 10 nM raloxifene and 81.57% 100 nM raloxifenecotreatment. Raloxifene cotreatment reduced superoxide production by 72.72% and peroxide production by57%. Mitochondrial mass was preserved by 47.4%, 75.5%, and 89% in T98G cells exposed to 6-hour oxygenglucosedeprivation followed by 3, 6, and 9 hours of reoxygenation, respectively. Conclusions. Raloxifeneimproved cell survival and mitochondrial membrane potential, and reduced lipid peroxidation and reactiveoxygen species (ROS) production, suggesting a direct effect on mitochondria. Raloxifene protected the oxygenglucose-deprived astrocyte cells used to mimic hypoxic-ischemic brain injury in this study.
Fil: Toro Urrego, Nicolas. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Luaces, Juan Pablo. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bordet, Sofía. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Otero-losada, Matilde Estela. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Capani, Francisco. Universidad Autónoma de Chile; Chile. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
RALOXIFENE
NEUROPROTECTION
ASTROCYTES GLUCOSE DEPRIVATION
OXYGEN DEPRIVATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/241277
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/241277
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain InjuryToro Urrego, NicolasLuaces, Juan PabloBordet, SofíaOtero-losada, Matilde EstelaCapani, FranciscoRALOXIFENENEUROPROTECTIONASTROCYTES GLUCOSE DEPRIVATIONOXYGEN DEPRIVATIONhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background. Hypoxic-ischemic brain injury is one primary cause of long-term neurologicaldisability, morbidity, and death worldwide. The decrease in blood flow and oxygen concentration leads toinsufficient nutrient supply to the brain, energy depletion, increased free radical generation, and mitochondrialdysfunction. Perinatal asphyxia — the oxygen supply suspension near birth-time — causes hypoxic-ischemicbrain injury and is a major risk factor for neurodevelopmental damage. In pathological scenarios, raloxifene, aselective estrogen receptor modulator, has shown neuroprotective effects. Purpose. To examine whetherraloxifene showed neuroprotection in an oxygen-glucose deprivation/reoxygenation astrocyte cell model.Methods. T98G cells in culture were treated with a glucose-free DMEM medium and incubated at 37ºC in ahypoxia chamber with 1% O2 for 3, 6, 12, and 24 hours. Cultures were supplemented with raloxifene 1, 10, and100 nM during both glucose and oxygen deprivation and reoxygenation periods. Results. Raloxifene 100 nMand 10 nM improved cell survival — 65.34% and 70.56% — respectively compared to the control cell groups.Mitochondrial membrane potential was preserved by 58.9% 10 nM raloxifene and 81.57% 100 nM raloxifenecotreatment. Raloxifene cotreatment reduced superoxide production by 72.72% and peroxide production by57%. Mitochondrial mass was preserved by 47.4%, 75.5%, and 89% in T98G cells exposed to 6-hour oxygenglucosedeprivation followed by 3, 6, and 9 hours of reoxygenation, respectively. Conclusions. Raloxifeneimproved cell survival and mitochondrial membrane potential, and reduced lipid peroxidation and reactiveoxygen species (ROS) production, suggesting a direct effect on mitochondria. Raloxifene protected the oxygenglucose-deprived astrocyte cells used to mimic hypoxic-ischemic brain injury in this study.Fil: Toro Urrego, Nicolas. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Luaces, Juan Pablo. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bordet, Sofía. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Otero-losada, Matilde Estela. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Capani, Francisco. Universidad Autónoma de Chile; Chile. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaMultidisciplinary Digital Publishing Institute2024-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/241277Toro Urrego, Nicolas; Luaces, Juan Pablo; Bordet, Sofía; Otero-losada, Matilde Estela; Capani, Francisco; Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury; Multidisciplinary Digital Publishing Institute; Preprints.org; 5-2024; 1-152310-287XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.preprints.org/manuscript/202405.1327/v1info:eu-repo/semantics/altIdentifier/doi/10.20944/preprints202405.1327.v1info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:26Zoai:ri.conicet.gov.ar:11336/241277instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:59:27.196CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury
title Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury
spellingShingle Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury
Toro Urrego, Nicolas
RALOXIFENE
NEUROPROTECTION
ASTROCYTES GLUCOSE DEPRIVATION
OXYGEN DEPRIVATION
title_short Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury
title_full Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury
title_fullStr Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury
title_full_unstemmed Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury
title_sort Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury
dc.creator.none.fl_str_mv Toro Urrego, Nicolas
Luaces, Juan Pablo
Bordet, Sofía
Otero-losada, Matilde Estela
Capani, Francisco
author Toro Urrego, Nicolas
author_facet Toro Urrego, Nicolas
Luaces, Juan Pablo
Bordet, Sofía
Otero-losada, Matilde Estela
Capani, Francisco
author_role author
author2 Luaces, Juan Pablo
Bordet, Sofía
Otero-losada, Matilde Estela
Capani, Francisco
author2_role author
author
author
author
dc.subject.none.fl_str_mv RALOXIFENE
NEUROPROTECTION
ASTROCYTES GLUCOSE DEPRIVATION
OXYGEN DEPRIVATION
topic RALOXIFENE
NEUROPROTECTION
ASTROCYTES GLUCOSE DEPRIVATION
OXYGEN DEPRIVATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background. Hypoxic-ischemic brain injury is one primary cause of long-term neurologicaldisability, morbidity, and death worldwide. The decrease in blood flow and oxygen concentration leads toinsufficient nutrient supply to the brain, energy depletion, increased free radical generation, and mitochondrialdysfunction. Perinatal asphyxia — the oxygen supply suspension near birth-time — causes hypoxic-ischemicbrain injury and is a major risk factor for neurodevelopmental damage. In pathological scenarios, raloxifene, aselective estrogen receptor modulator, has shown neuroprotective effects. Purpose. To examine whetherraloxifene showed neuroprotection in an oxygen-glucose deprivation/reoxygenation astrocyte cell model.Methods. T98G cells in culture were treated with a glucose-free DMEM medium and incubated at 37ºC in ahypoxia chamber with 1% O2 for 3, 6, 12, and 24 hours. Cultures were supplemented with raloxifene 1, 10, and100 nM during both glucose and oxygen deprivation and reoxygenation periods. Results. Raloxifene 100 nMand 10 nM improved cell survival — 65.34% and 70.56% — respectively compared to the control cell groups.Mitochondrial membrane potential was preserved by 58.9% 10 nM raloxifene and 81.57% 100 nM raloxifenecotreatment. Raloxifene cotreatment reduced superoxide production by 72.72% and peroxide production by57%. Mitochondrial mass was preserved by 47.4%, 75.5%, and 89% in T98G cells exposed to 6-hour oxygenglucosedeprivation followed by 3, 6, and 9 hours of reoxygenation, respectively. Conclusions. Raloxifeneimproved cell survival and mitochondrial membrane potential, and reduced lipid peroxidation and reactiveoxygen species (ROS) production, suggesting a direct effect on mitochondria. Raloxifene protected the oxygenglucose-deprived astrocyte cells used to mimic hypoxic-ischemic brain injury in this study.
Fil: Toro Urrego, Nicolas. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Luaces, Juan Pablo. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bordet, Sofía. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Otero-losada, Matilde Estela. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Capani, Francisco. Universidad Autónoma de Chile; Chile. Universidad Abierta Interamericana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Background. Hypoxic-ischemic brain injury is one primary cause of long-term neurologicaldisability, morbidity, and death worldwide. The decrease in blood flow and oxygen concentration leads toinsufficient nutrient supply to the brain, energy depletion, increased free radical generation, and mitochondrialdysfunction. Perinatal asphyxia — the oxygen supply suspension near birth-time — causes hypoxic-ischemicbrain injury and is a major risk factor for neurodevelopmental damage. In pathological scenarios, raloxifene, aselective estrogen receptor modulator, has shown neuroprotective effects. Purpose. To examine whetherraloxifene showed neuroprotection in an oxygen-glucose deprivation/reoxygenation astrocyte cell model.Methods. T98G cells in culture were treated with a glucose-free DMEM medium and incubated at 37ºC in ahypoxia chamber with 1% O2 for 3, 6, 12, and 24 hours. Cultures were supplemented with raloxifene 1, 10, and100 nM during both glucose and oxygen deprivation and reoxygenation periods. Results. Raloxifene 100 nMand 10 nM improved cell survival — 65.34% and 70.56% — respectively compared to the control cell groups.Mitochondrial membrane potential was preserved by 58.9% 10 nM raloxifene and 81.57% 100 nM raloxifenecotreatment. Raloxifene cotreatment reduced superoxide production by 72.72% and peroxide production by57%. Mitochondrial mass was preserved by 47.4%, 75.5%, and 89% in T98G cells exposed to 6-hour oxygenglucosedeprivation followed by 3, 6, and 9 hours of reoxygenation, respectively. Conclusions. Raloxifeneimproved cell survival and mitochondrial membrane potential, and reduced lipid peroxidation and reactiveoxygen species (ROS) production, suggesting a direct effect on mitochondria. Raloxifene protected the oxygenglucose-deprived astrocyte cells used to mimic hypoxic-ischemic brain injury in this study.
publishDate 2024
dc.date.none.fl_str_mv 2024-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/241277
Toro Urrego, Nicolas; Luaces, Juan Pablo; Bordet, Sofía; Otero-losada, Matilde Estela; Capani, Francisco; Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury; Multidisciplinary Digital Publishing Institute; Preprints.org; 5-2024; 1-15
2310-287X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/241277
identifier_str_mv Toro Urrego, Nicolas; Luaces, Juan Pablo; Bordet, Sofía; Otero-losada, Matilde Estela; Capani, Francisco; Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury; Multidisciplinary Digital Publishing Institute; Preprints.org; 5-2024; 1-15
2310-287X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.preprints.org/manuscript/202405.1327/v1
info:eu-repo/semantics/altIdentifier/doi/10.20944/preprints202405.1327.v1
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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