Tetrandrine concentrations not affecting oxidative phosphorylation protect rat liver mitochondria from oxidative stress
Autor(a) principal: | |
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Data de Publicação: | 2006 |
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/10316/5341 https://doi.org/10.1016/j.mito.2006.06.002 |
Resumo: | The effects of tetrandrine (6,6', 7,12-tetramethoxy-2, 2'-dimethyl-berbaman) on the mitochondrial function were assessed on oxidative stress, mitochondrial permeability transition (MPT), and bioenergetics of rat liver mitochondria. At concentrations lower than 100 nmol/mg protein, tetrandrine decreased the hydrogen peroxide formation, the extent of lipid peroxidation, the susceptibility to Ca2+-induced opening of MPT pore, and inhibited the inner membrane anion channel activity, not significantly affecting the mitochondrial bioenergetics. High tetrandrine concentrations (100-300 nmol/mg protein) stimulated succinate-dependent state 4 respiration, while some inhibition was observed for state 3 and p-trifluoromethoxyphenylhydrazone-uncoupled respirations. The respiratory control ratio and the transmembrane potential were depressed but the adenosine diphosphate to oxygen (ADP/O) ratio was less affected. A slight increase of the inner mitochondrial membrane permeability to H+ and K+ by tetrandrine was also observed. It was concluded that low concentrations of tetrandrine afford protection against liver mitochondria injury promoted by oxidative-stress events, such as hydrogen peroxide production, lipid peroxidation, and induction of MPT. Conversely, high tetrandrine concentrations revealed toxicological effects expressed by interference with mitochondrial bioenergetics, as a consequence of some inner membrane permeability to H+ and K+ and inhibition of the electron flux in the respiratory chain. The direct immediate protective role of tetrandrine against mitochondrial oxidative stress may be relevant to clarify the mechanisms responsible for its multiple pharmacological actions. |
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Tetrandrine concentrations not affecting oxidative phosphorylation protect rat liver mitochondria from oxidative stressBisbenzylisoquinoline alkaloideMitochondrial bioenergeticsPermeability transition poreTetrandrineThe effects of tetrandrine (6,6', 7,12-tetramethoxy-2, 2'-dimethyl-berbaman) on the mitochondrial function were assessed on oxidative stress, mitochondrial permeability transition (MPT), and bioenergetics of rat liver mitochondria. At concentrations lower than 100 nmol/mg protein, tetrandrine decreased the hydrogen peroxide formation, the extent of lipid peroxidation, the susceptibility to Ca2+-induced opening of MPT pore, and inhibited the inner membrane anion channel activity, not significantly affecting the mitochondrial bioenergetics. High tetrandrine concentrations (100-300 nmol/mg protein) stimulated succinate-dependent state 4 respiration, while some inhibition was observed for state 3 and p-trifluoromethoxyphenylhydrazone-uncoupled respirations. The respiratory control ratio and the transmembrane potential were depressed but the adenosine diphosphate to oxygen (ADP/O) ratio was less affected. A slight increase of the inner mitochondrial membrane permeability to H+ and K+ by tetrandrine was also observed. It was concluded that low concentrations of tetrandrine afford protection against liver mitochondria injury promoted by oxidative-stress events, such as hydrogen peroxide production, lipid peroxidation, and induction of MPT. Conversely, high tetrandrine concentrations revealed toxicological effects expressed by interference with mitochondrial bioenergetics, as a consequence of some inner membrane permeability to H+ and K+ and inhibition of the electron flux in the respiratory chain. The direct immediate protective role of tetrandrine against mitochondrial oxidative stress may be relevant to clarify the mechanisms responsible for its multiple pharmacological actions.http://www.sciencedirect.com/science/article/B6W8G-4K8Y99X-1/1/34bae8ec6f49b23b674ee4e90404f49f2006info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/5341http://hdl.handle.net/10316/5341https://doi.org/10.1016/j.mito.2006.06.002engMitochondrion. 6:4 (2006) 176-185Fernandes, Maria A. S.Custódio, José B. A.Santos, Maria S.Moreno, António J. M.Vicente, Joaquim A. F.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:RCAAP2020-11-06T16:49:15Zoai:estudogeral.uc.pt:10316/5341Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:55:36.187812Repositório 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 |
Tetrandrine concentrations not affecting oxidative phosphorylation protect rat liver mitochondria from oxidative stress |
title |
Tetrandrine concentrations not affecting oxidative phosphorylation protect rat liver mitochondria from oxidative stress |
spellingShingle |
Tetrandrine concentrations not affecting oxidative phosphorylation protect rat liver mitochondria from oxidative stress Fernandes, Maria A. S. Bisbenzylisoquinoline alkaloide Mitochondrial bioenergetics Permeability transition pore Tetrandrine |
title_short |
Tetrandrine concentrations not affecting oxidative phosphorylation protect rat liver mitochondria from oxidative stress |
title_full |
Tetrandrine concentrations not affecting oxidative phosphorylation protect rat liver mitochondria from oxidative stress |
title_fullStr |
Tetrandrine concentrations not affecting oxidative phosphorylation protect rat liver mitochondria from oxidative stress |
title_full_unstemmed |
Tetrandrine concentrations not affecting oxidative phosphorylation protect rat liver mitochondria from oxidative stress |
title_sort |
Tetrandrine concentrations not affecting oxidative phosphorylation protect rat liver mitochondria from oxidative stress |
author |
Fernandes, Maria A. S. |
author_facet |
Fernandes, Maria A. S. Custódio, José B. A. Santos, Maria S. Moreno, António J. M. Vicente, Joaquim A. F. |
author_role |
author |
author2 |
Custódio, José B. A. Santos, Maria S. Moreno, António J. M. Vicente, Joaquim A. F. |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Fernandes, Maria A. S. Custódio, José B. A. Santos, Maria S. Moreno, António J. M. Vicente, Joaquim A. F. |
dc.subject.por.fl_str_mv |
Bisbenzylisoquinoline alkaloide Mitochondrial bioenergetics Permeability transition pore Tetrandrine |
topic |
Bisbenzylisoquinoline alkaloide Mitochondrial bioenergetics Permeability transition pore Tetrandrine |
description |
The effects of tetrandrine (6,6', 7,12-tetramethoxy-2, 2'-dimethyl-berbaman) on the mitochondrial function were assessed on oxidative stress, mitochondrial permeability transition (MPT), and bioenergetics of rat liver mitochondria. At concentrations lower than 100 nmol/mg protein, tetrandrine decreased the hydrogen peroxide formation, the extent of lipid peroxidation, the susceptibility to Ca2+-induced opening of MPT pore, and inhibited the inner membrane anion channel activity, not significantly affecting the mitochondrial bioenergetics. High tetrandrine concentrations (100-300 nmol/mg protein) stimulated succinate-dependent state 4 respiration, while some inhibition was observed for state 3 and p-trifluoromethoxyphenylhydrazone-uncoupled respirations. The respiratory control ratio and the transmembrane potential were depressed but the adenosine diphosphate to oxygen (ADP/O) ratio was less affected. A slight increase of the inner mitochondrial membrane permeability to H+ and K+ by tetrandrine was also observed. It was concluded that low concentrations of tetrandrine afford protection against liver mitochondria injury promoted by oxidative-stress events, such as hydrogen peroxide production, lipid peroxidation, and induction of MPT. Conversely, high tetrandrine concentrations revealed toxicological effects expressed by interference with mitochondrial bioenergetics, as a consequence of some inner membrane permeability to H+ and K+ and inhibition of the electron flux in the respiratory chain. The direct immediate protective role of tetrandrine against mitochondrial oxidative stress may be relevant to clarify the mechanisms responsible for its multiple pharmacological actions. |
publishDate |
2006 |
dc.date.none.fl_str_mv |
2006 |
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/10316/5341 http://hdl.handle.net/10316/5341 https://doi.org/10.1016/j.mito.2006.06.002 |
url |
http://hdl.handle.net/10316/5341 https://doi.org/10.1016/j.mito.2006.06.002 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Mitochondrion. 6:4 (2006) 176-185 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
aplication/PDF |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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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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1799133842741657600 |