Mitochondrially-mediated toxicity of bile acids
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/10316/5378 https://doi.org/10.1016/j.tox.2004.06.001 |
Resumo: | In the healthy hepatocyte, uptake of bile acids across the basolateral membrane and export via the canalicular export pump, are tightly coupled. Impairment of bile formation or excretion results in cholestasis, characterized by accumulation of bile acids in systemic blood and within the hepatocyte. When the concentration of bile acids exceeds the binding capacity of the binding protein located in the cytosol of the hepatocyte, bile acids induce apoptosis and necrosis, by damage to mitochondria. Mitochondria play a central role on the toxicity of bile acids. In this article, we review the published literature regarding bile acid effects on cell function, especially at the mitochondrial level. In patients with cholestatic liver disease, the extent of hepatocyte damage caused by intracellular accumulation of bile acids appears to be delayed by ingesting a hydrophilic bile acid. However, its effects on disease progression are not completely clarified. Therefore, identification of the mechanisms of cell injury will be of clinical utility, helping in the development of new therapeutic strategies. The goal of this review is to include a fresh consideration of all possible targets and integrating pathways that are involved in cholestasis, as well as in the benefits of bile acid therapy. |
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Mitochondrially-mediated toxicity of bile acidsBile acidsCholestasisMitochondriaIn the healthy hepatocyte, uptake of bile acids across the basolateral membrane and export via the canalicular export pump, are tightly coupled. Impairment of bile formation or excretion results in cholestasis, characterized by accumulation of bile acids in systemic blood and within the hepatocyte. When the concentration of bile acids exceeds the binding capacity of the binding protein located in the cytosol of the hepatocyte, bile acids induce apoptosis and necrosis, by damage to mitochondria. Mitochondria play a central role on the toxicity of bile acids. In this article, we review the published literature regarding bile acid effects on cell function, especially at the mitochondrial level. In patients with cholestatic liver disease, the extent of hepatocyte damage caused by intracellular accumulation of bile acids appears to be delayed by ingesting a hydrophilic bile acid. However, its effects on disease progression are not completely clarified. Therefore, identification of the mechanisms of cell injury will be of clinical utility, helping in the development of new therapeutic strategies. The goal of this review is to include a fresh consideration of all possible targets and integrating pathways that are involved in cholestasis, as well as in the benefits of bile acid therapy.http://www.sciencedirect.com/science/article/B6TCN-4CYPX2G-3/1/2c182e514fe10b772c8efd9b763303a32004info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/5378http://hdl.handle.net/10316/5378https://doi.org/10.1016/j.tox.2004.06.001engToxicology. 203:1-3 (2004) 1-15Palmeira, Carlos M.Rolo, Anabela P.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:RCAAP2021-10-07T10:32:22Zoai:estudogeral.uc.pt:10316/5378Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:55:27.806051Repositório 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 |
Mitochondrially-mediated toxicity of bile acids |
title |
Mitochondrially-mediated toxicity of bile acids |
spellingShingle |
Mitochondrially-mediated toxicity of bile acids Palmeira, Carlos M. Bile acids Cholestasis Mitochondria |
title_short |
Mitochondrially-mediated toxicity of bile acids |
title_full |
Mitochondrially-mediated toxicity of bile acids |
title_fullStr |
Mitochondrially-mediated toxicity of bile acids |
title_full_unstemmed |
Mitochondrially-mediated toxicity of bile acids |
title_sort |
Mitochondrially-mediated toxicity of bile acids |
author |
Palmeira, Carlos M. |
author_facet |
Palmeira, Carlos M. Rolo, Anabela P. |
author_role |
author |
author2 |
Rolo, Anabela P. |
author2_role |
author |
dc.contributor.author.fl_str_mv |
Palmeira, Carlos M. Rolo, Anabela P. |
dc.subject.por.fl_str_mv |
Bile acids Cholestasis Mitochondria |
topic |
Bile acids Cholestasis Mitochondria |
description |
In the healthy hepatocyte, uptake of bile acids across the basolateral membrane and export via the canalicular export pump, are tightly coupled. Impairment of bile formation or excretion results in cholestasis, characterized by accumulation of bile acids in systemic blood and within the hepatocyte. When the concentration of bile acids exceeds the binding capacity of the binding protein located in the cytosol of the hepatocyte, bile acids induce apoptosis and necrosis, by damage to mitochondria. Mitochondria play a central role on the toxicity of bile acids. In this article, we review the published literature regarding bile acid effects on cell function, especially at the mitochondrial level. In patients with cholestatic liver disease, the extent of hepatocyte damage caused by intracellular accumulation of bile acids appears to be delayed by ingesting a hydrophilic bile acid. However, its effects on disease progression are not completely clarified. Therefore, identification of the mechanisms of cell injury will be of clinical utility, helping in the development of new therapeutic strategies. The goal of this review is to include a fresh consideration of all possible targets and integrating pathways that are involved in cholestasis, as well as in the benefits of bile acid therapy. |
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/10316/5378 http://hdl.handle.net/10316/5378 https://doi.org/10.1016/j.tox.2004.06.001 |
url |
http://hdl.handle.net/10316/5378 https://doi.org/10.1016/j.tox.2004.06.001 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Toxicology. 203:1-3 (2004) 1-15 |
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 |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
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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1799133841700421632 |