Hydroxytamoxifen protects against oxidative stress in brain mitochondria
Autor(a) principal: | |
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Data de Publicação: | 2004 |
Outros Autores: | , , |
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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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 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
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 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
aplication/PDF |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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