Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity

Detalhes bibliográficos
Autor(a) principal: Oliveira, Paulo J.
Data de Publicação: 2004
Outros Autores: Bjork, James A., Santos, Maria S., Leino, Richard L., Froberg, M. Kent, Moreno, António J., Wallace, Kendall B.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/5379
https://doi.org/10.1016/j.taap.2004.04.005
Resumo: The cardiotoxicity associated with doxorubicin (DOX) therapy limits the total cumulative dose and therapeutic success of active anticancer chemotherapy. Cardiac mitochondria are implicated as primary targets for DOX toxicity, which is believed to be mediated by the generation of highly reactive free radical species of oxygen from complex I of the mitochondrial electron transport chain. The objective of this study was to determine if the protection demonstrated by carvedilol (CV), a [beta]-adrenergic receptor antagonist with strong antioxidant properties, against DOX-induced mitochondrial-mediated cardiomyopathy [Toxicol. Appl. Pharmacol. 185 (2002) 218] is attributable to its antioxidant properties or its [beta]-adrenergic receptor antagonism. Our results confirm that DOX induces oxidative stress, mitochondrial dysfunction, and histopathological lesions in the cardiac tissue, all of which are inhibited by carvedilol. In contrast, atenolol (AT), a [beta]-adrenergic receptor antagonist lacking antioxidant properties, preserved phosphate energy charge but failed to protect against any of the indexes of DOX-induced oxidative mitochondrial toxicity. We therefore conclude that the cardioprotective effects of carvedilol against DOX-induced mitochondrial cardiotoxicity are due to its inherent antioxidant activity and not to its [beta]-adrenergic receptor antagonism.
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spelling Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicityMitochondriaDoxorubicinCarvedilolAtenololPermeability transition poreOxidative damageMitochondrionopathyThe cardiotoxicity associated with doxorubicin (DOX) therapy limits the total cumulative dose and therapeutic success of active anticancer chemotherapy. Cardiac mitochondria are implicated as primary targets for DOX toxicity, which is believed to be mediated by the generation of highly reactive free radical species of oxygen from complex I of the mitochondrial electron transport chain. The objective of this study was to determine if the protection demonstrated by carvedilol (CV), a [beta]-adrenergic receptor antagonist with strong antioxidant properties, against DOX-induced mitochondrial-mediated cardiomyopathy [Toxicol. Appl. Pharmacol. 185 (2002) 218] is attributable to its antioxidant properties or its [beta]-adrenergic receptor antagonism. Our results confirm that DOX induces oxidative stress, mitochondrial dysfunction, and histopathological lesions in the cardiac tissue, all of which are inhibited by carvedilol. In contrast, atenolol (AT), a [beta]-adrenergic receptor antagonist lacking antioxidant properties, preserved phosphate energy charge but failed to protect against any of the indexes of DOX-induced oxidative mitochondrial toxicity. We therefore conclude that the cardioprotective effects of carvedilol against DOX-induced mitochondrial cardiotoxicity are due to its inherent antioxidant activity and not to its [beta]-adrenergic receptor antagonism.http://www.sciencedirect.com/science/article/B6WXH-4CP69N9-2/1/af6fb8993cd9345f9ad3e7303bff3b0a2004info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/5379http://hdl.handle.net/10316/5379https://doi.org/10.1016/j.taap.2004.04.005engToxicology and Applied Pharmacology. 200:2 (2004) 159-168Oliveira, Paulo J.Bjork, James A.Santos, Maria S.Leino, Richard L.Froberg, M. KentMoreno, António J.Wallace, Kendall B.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:RCAAP2021-10-06T09:57:20Zoai:estudogeral.uc.pt:10316/5379Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:55:27.857481Repositório 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 Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity
title Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity
spellingShingle Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity
Oliveira, Paulo J.
Mitochondria
Doxorubicin
Carvedilol
Atenolol
Permeability transition pore
Oxidative damage
Mitochondrionopathy
title_short Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity
title_full Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity
title_fullStr Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity
title_full_unstemmed Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity
title_sort Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac mitochondrial toxicity
author Oliveira, Paulo J.
author_facet Oliveira, Paulo J.
Bjork, James A.
Santos, Maria S.
Leino, Richard L.
Froberg, M. Kent
Moreno, António J.
Wallace, Kendall B.
author_role author
author2 Bjork, James A.
Santos, Maria S.
Leino, Richard L.
Froberg, M. Kent
Moreno, António J.
Wallace, Kendall B.
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Oliveira, Paulo J.
Bjork, James A.
Santos, Maria S.
Leino, Richard L.
Froberg, M. Kent
Moreno, António J.
Wallace, Kendall B.
dc.subject.por.fl_str_mv Mitochondria
Doxorubicin
Carvedilol
Atenolol
Permeability transition pore
Oxidative damage
Mitochondrionopathy
topic Mitochondria
Doxorubicin
Carvedilol
Atenolol
Permeability transition pore
Oxidative damage
Mitochondrionopathy
description The cardiotoxicity associated with doxorubicin (DOX) therapy limits the total cumulative dose and therapeutic success of active anticancer chemotherapy. Cardiac mitochondria are implicated as primary targets for DOX toxicity, which is believed to be mediated by the generation of highly reactive free radical species of oxygen from complex I of the mitochondrial electron transport chain. The objective of this study was to determine if the protection demonstrated by carvedilol (CV), a [beta]-adrenergic receptor antagonist with strong antioxidant properties, against DOX-induced mitochondrial-mediated cardiomyopathy [Toxicol. Appl. Pharmacol. 185 (2002) 218] is attributable to its antioxidant properties or its [beta]-adrenergic receptor antagonism. Our results confirm that DOX induces oxidative stress, mitochondrial dysfunction, and histopathological lesions in the cardiac tissue, all of which are inhibited by carvedilol. In contrast, atenolol (AT), a [beta]-adrenergic receptor antagonist lacking antioxidant properties, preserved phosphate energy charge but failed to protect against any of the indexes of DOX-induced oxidative mitochondrial toxicity. We therefore conclude that the cardioprotective effects of carvedilol against DOX-induced mitochondrial cardiotoxicity are due to its inherent antioxidant activity and not to its [beta]-adrenergic receptor antagonism.
publishDate 2004
dc.date.none.fl_str_mv 2004
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10316/5379
http://hdl.handle.net/10316/5379
https://doi.org/10.1016/j.taap.2004.04.005
url http://hdl.handle.net/10316/5379
https://doi.org/10.1016/j.taap.2004.04.005
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Toxicology and Applied Pharmacology. 200:2 (2004) 159-168
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