Hydroxytamoxifen protects against oxidative stress in brain mitochondria

Detalhes bibliográficos
Autor(a) principal: Moreira, Paula I.
Data de Publicação: 2004
Outros Autores: Custódio, José B., Oliveira, Catarina R., Santos, Maria S.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/5388
https://doi.org/10.1016/j.bcp.2004.03.019
Resumo: This study evaluated the effect of hydroxytamoxifen, the major active metabolite of tamoxifen (synthetic, nonsteroidal antiestrogen drug), on the function of brain mitochondria. We observed that only high concentrations of hydroxytamoxifen (60 nmol/mg protein) induced a significant decrease in RCR, while ADP/O ratio remained statistically unchanged. Similarly, only the highest concentration of hydroxytamoxifen (60 nmol/mg protein) affected the phosphorylative capacity of brain mitochondria, characterized by a decrease in the repolarization level and an increase in the repolarization lag phase. We observed that all the concentrations of hydroxytamoxifen tested (7.5, 15 and 30 nmol/mg protein) prevented lipid peroxidation induced by the oxidant pair ADP/Fe2+. Furthermore, through the analyses of calcium fluxes and mitochondrial transmembrane potential parameters, we observed that hydroxytamoxifen (30 nmol/mg protein) exerted some protection against pore opening, although in a less extension than that promoted by cyclosporin A, the specific inhibitor of the mitochondrial permeability transition pore. However, in the presence of hydroxytamoxifen plus cyclosporin A, the protection observed was significantly higher when compared with that induced by both agents alone.
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spelling Hydroxytamoxifen protects against oxidative stress in brain mitochondriaCalciumHydroxytamoxifenLipid peroxidationMitochondrial permeability transitionNeuroprotectionThis study evaluated the effect of hydroxytamoxifen, the major active metabolite of tamoxifen (synthetic, nonsteroidal antiestrogen drug), on the function of brain mitochondria. We observed that only high concentrations of hydroxytamoxifen (60 nmol/mg protein) induced a significant decrease in RCR, while ADP/O ratio remained statistically unchanged. Similarly, only the highest concentration of hydroxytamoxifen (60 nmol/mg protein) affected the phosphorylative capacity of brain mitochondria, characterized by a decrease in the repolarization level and an increase in the repolarization lag phase. We observed that all the concentrations of hydroxytamoxifen tested (7.5, 15 and 30 nmol/mg protein) prevented lipid peroxidation induced by the oxidant pair ADP/Fe2+. Furthermore, through the analyses of calcium fluxes and mitochondrial transmembrane potential parameters, we observed that hydroxytamoxifen (30 nmol/mg protein) exerted some protection against pore opening, although in a less extension than that promoted by cyclosporin A, the specific inhibitor of the mitochondrial permeability transition pore. However, in the presence of hydroxytamoxifen plus cyclosporin A, the protection observed was significantly higher when compared with that induced by both agents alone.http://www.sciencedirect.com/science/article/B6T4P-4CBDG4X-1/1/ee8ed2d61b5af16897a3fcca2a769b932004info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/5388http://hdl.handle.net/10316/5388https://doi.org/10.1016/j.bcp.2004.03.019engBiochemical Pharmacology. 68:1 (2004) 195-204Moreira, Paula I.Custódio, José B.Oliveira, Catarina R.Santos, Maria S.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2021-02-26T11:01:37Zoai:estudogeral.uc.pt:10316/5388Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:55:28.192796Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Hydroxytamoxifen protects against oxidative stress in brain mitochondria
title Hydroxytamoxifen protects against oxidative stress in brain mitochondria
spellingShingle Hydroxytamoxifen protects against oxidative stress in brain mitochondria
Moreira, Paula I.
Calcium
Hydroxytamoxifen
Lipid peroxidation
Mitochondrial permeability transition
Neuroprotection
title_short Hydroxytamoxifen protects against oxidative stress in brain mitochondria
title_full Hydroxytamoxifen protects against oxidative stress in brain mitochondria
title_fullStr Hydroxytamoxifen protects against oxidative stress in brain mitochondria
title_full_unstemmed Hydroxytamoxifen protects against oxidative stress in brain mitochondria
title_sort Hydroxytamoxifen protects against oxidative stress in brain mitochondria
author Moreira, Paula I.
author_facet Moreira, Paula I.
Custódio, José B.
Oliveira, Catarina R.
Santos, Maria S.
author_role author
author2 Custódio, José B.
Oliveira, Catarina R.
Santos, Maria S.
author2_role author
author
author
dc.contributor.author.fl_str_mv Moreira, Paula I.
Custódio, José B.
Oliveira, Catarina R.
Santos, Maria S.
dc.subject.por.fl_str_mv Calcium
Hydroxytamoxifen
Lipid peroxidation
Mitochondrial permeability transition
Neuroprotection
topic Calcium
Hydroxytamoxifen
Lipid peroxidation
Mitochondrial permeability transition
Neuroprotection
description This study evaluated the effect of hydroxytamoxifen, the major active metabolite of tamoxifen (synthetic, nonsteroidal antiestrogen drug), on the function of brain mitochondria. We observed that only high concentrations of hydroxytamoxifen (60 nmol/mg protein) induced a significant decrease in RCR, while ADP/O ratio remained statistically unchanged. Similarly, only the highest concentration of hydroxytamoxifen (60 nmol/mg protein) affected the phosphorylative capacity of brain mitochondria, characterized by a decrease in the repolarization level and an increase in the repolarization lag phase. We observed that all the concentrations of hydroxytamoxifen tested (7.5, 15 and 30 nmol/mg protein) prevented lipid peroxidation induced by the oxidant pair ADP/Fe2+. Furthermore, through the analyses of calcium fluxes and mitochondrial transmembrane potential parameters, we observed that hydroxytamoxifen (30 nmol/mg protein) exerted some protection against pore opening, although in a less extension than that promoted by cyclosporin A, the specific inhibitor of the mitochondrial permeability transition pore. However, in the presence of hydroxytamoxifen plus cyclosporin A, the protection observed was significantly higher when compared with that induced by both agents alone.
publishDate 2004
dc.date.none.fl_str_mv 2004
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10316/5388
http://hdl.handle.net/10316/5388
https://doi.org/10.1016/j.bcp.2004.03.019
url http://hdl.handle.net/10316/5388
https://doi.org/10.1016/j.bcp.2004.03.019
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Biochemical Pharmacology. 68:1 (2004) 195-204
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