Raloxifene protects oxygen-glucose-deprived astrocyte cells used to mimic hypoxic-ischemic brain injury

Perinatal asphyxia (PA) is a clinical condition characterized by oxygen supply suspension before, during, or immediately after birth, and it is an important risk factor for neurodevelopmental damage. Its estimated 1/1000 live births incidence in developed countries rises to 5–10-fold in developing c...

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Autores principales: Toro-Urrego, Nicolás, Luaces, Juan P., Kobiec, Tamara, Udovin, Lucas, Bordet, Sofía, Otero-Losada, Matilde, Capani, Francisco
Formato: Artículo
Lenguaje:Inglés
Publicado: MDPI 2025
Materias:
NEUROPROTECCION
RALOXIFENO
HIPOXIA
ASFIXIA PERINATAL
DAÑO CEREBRAL
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/20047
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-20047
record_format dspace
spelling I33-R139-123456789-200472025-07-09T05:01:21Z Raloxifene protects oxygen-glucose-deprived astrocyte cells used to mimic hypoxic-ischemic brain injury Toro-Urrego, Nicolás Luaces, Juan P. Kobiec, Tamara Udovin, Lucas Bordet, Sofía Otero-Losada, Matilde Capani, Francisco NEUROPROTECCION RALOXIFENO HIPOXIA ASFIXIA PERINATAL DAÑO CEREBRAL Perinatal asphyxia (PA) is a clinical condition characterized by oxygen supply suspension before, during, or immediately after birth, and it is an important risk factor for neurodevelopmental damage. Its estimated 1/1000 live births incidence in developed countries rises to 5–10-fold in developing countries. Schizophrenia, cerebral palsy, mental retardation, epilepsy, blindness, and others are among the highly disabling chronic pathologies associated with PA. However, so far, there is no effective therapy to neutralize or reduce PA-induced harm. Selective regulators of estrogen activity in tissues and selective estrogen receptor modulators like raloxifene have shown neuroprotective activity in different pathological scenarios. Their effect on PA is yet unknown. The purpose of this paper is to examine whether raloxifene showed neuroprotection in an oxygen–glucose deprivation/reoxygenation astrocyte cell model. To study this issue, T98G cells in culture were treated with a glucose-free DMEM medium and incubated at 37 °C in a hypoxia chamber with 1% O2 for 3, 6, 12, and 24 h. Cultures were supplemented with raloxifene 10, and 100 nM during both glucose and oxygen deprivation and reoxygenation periods. Raloxifene 100 nM and 10 nM improved cell survival—65.34% and 70.56%, respectively, compared with the control cell groups. Mitochondrial membrane potential was preserved by 58.9% 10 nM raloxifene and 81.57% 100 nM raloxifene cotreatment. Raloxifene co-treatment reduced superoxide production by 72.72% and peroxide production by 57%. Mitochondrial mass was preserved by 47.4%, 75.5%, and 89% in T98G cells exposed to 6-h oxygen–glucose deprivation followed by 3, 6, and 9 h of reoxygenation, respectively. Therefore, raloxifene improved cell survival and mitochondrial membrane potential and reduced lipid peroxidation and reactive oxygen species (ROS) production, suggesting a direct effect on mitochondria. In this study, raloxifene protected oxygen–glucose-deprived astrocyte cells, used to mimic hypoxic–ischemic brain injury. Two examiners performed the qualitative assessment in a double-blind fashion. 2025-07-08T18:14:41Z 2025-07-08T18:14:41Z 2024 Artículo 1422-0067 https://repositorio.uca.edu.ar/handle/123456789/20047 10.3390/ ijms252212121 eng Atribución-NoComercial-CompartirIgual 4.0 Internacional http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf MDPI International Journal of Molecular Sciences. 25, 2024.
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic NEUROPROTECCION
RALOXIFENO
HIPOXIA
ASFIXIA PERINATAL
DAÑO CEREBRAL
spellingShingle NEUROPROTECCION
RALOXIFENO
HIPOXIA
ASFIXIA PERINATAL
DAÑO CEREBRAL
Toro-Urrego, Nicolás
Luaces, Juan P.
Kobiec, Tamara
Udovin, Lucas
Bordet, Sofía
Otero-Losada, Matilde
Capani, Francisco
Raloxifene protects oxygen-glucose-deprived astrocyte cells used to mimic hypoxic-ischemic brain injury
topic_facet NEUROPROTECCION
RALOXIFENO
HIPOXIA
ASFIXIA PERINATAL
DAÑO CEREBRAL
description Perinatal asphyxia (PA) is a clinical condition characterized by oxygen supply suspension before, during, or immediately after birth, and it is an important risk factor for neurodevelopmental damage. Its estimated 1/1000 live births incidence in developed countries rises to 5–10-fold in developing countries. Schizophrenia, cerebral palsy, mental retardation, epilepsy, blindness, and others are among the highly disabling chronic pathologies associated with PA. However, so far, there is no effective therapy to neutralize or reduce PA-induced harm. Selective regulators of estrogen activity in tissues and selective estrogen receptor modulators like raloxifene have shown neuroprotective activity in different pathological scenarios. Their effect on PA is yet unknown. The purpose of this paper is to examine whether raloxifene showed neuroprotection in an oxygen–glucose deprivation/reoxygenation astrocyte cell model. To study this issue, T98G cells in culture were treated with a glucose-free DMEM medium and incubated at 37 °C in a hypoxia chamber with 1% O2 for 3, 6, 12, and 24 h. Cultures were supplemented with raloxifene 10, and 100 nM during both glucose and oxygen deprivation and reoxygenation periods. Raloxifene 100 nM and 10 nM improved cell survival—65.34% and 70.56%, respectively, compared with the control cell groups. Mitochondrial membrane potential was preserved by 58.9% 10 nM raloxifene and 81.57% 100 nM raloxifene cotreatment. Raloxifene co-treatment reduced superoxide production by 72.72% and peroxide production by 57%. Mitochondrial mass was preserved by 47.4%, 75.5%, and 89% in T98G cells exposed to 6-h oxygen–glucose deprivation followed by 3, 6, and 9 h of reoxygenation, respectively. Therefore, raloxifene improved cell survival and mitochondrial membrane potential and reduced lipid peroxidation and reactive oxygen species (ROS) production, suggesting a direct effect on mitochondria. In this study, raloxifene protected oxygen–glucose-deprived astrocyte cells, used to mimic hypoxic–ischemic brain injury. Two examiners performed the qualitative assessment in a double-blind fashion.
format Artículo
author Toro-Urrego, Nicolás
Luaces, Juan P.
Kobiec, Tamara
Udovin, Lucas
Bordet, Sofía
Otero-Losada, Matilde
Capani, Francisco
author_facet Toro-Urrego, Nicolás
Luaces, Juan P.
Kobiec, Tamara
Udovin, Lucas
Bordet, Sofía
Otero-Losada, Matilde
Capani, Francisco
author_sort Toro-Urrego, Nicolás
title Raloxifene protects oxygen-glucose-deprived astrocyte cells used to mimic hypoxic-ischemic brain injury
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
publisher MDPI
publishDate 2025
url https://repositorio.uca.edu.ar/handle/123456789/20047
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