Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid

Detalhes bibliográficos
Autor(a) principal: Teixeira, José
Data de Publicação: 2018
Outros Autores: Oliveira, Catarina, Cagide, Fernando, Amorim, Ricardo, Garrido, Jorge, Borges, Fernanda, Oliveira, Paulo J.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/107712
https://doi.org/10.1080/14756366.2018.1442831
Resumo: Pharmacological interventions targeting mitochondria present several barriers for a complete efficacy. Therefore, a new mitochondriotropic antioxidant (AntiOxBEN3) based on the dietary antioxidant gallic acid was developed. AntiOxBEN3 accumulated several thousand-fold inside isolated rat liver mitochondria, without causing disruption of the oxidative phosphorylation apparatus, as seen by the unchanged respiratory control ratio, phosphorylation efficiency, and transmembrane electric potential. AntiOxBEN3 showed also limited toxicity on human hepatocarcinoma cells. Moreover, AntiOxBEN3 presented robust iron-chelation and antioxidant properties in both isolated liver mitochondria and cultured rat and human cell lines. Along with its low toxicity profile and high antioxidant activity, AntiOxBEN3 strongly inhibited the calcium-dependent mitochondrial permeability transition pore (mPTP) opening. From our data, AntiOxBEN3 can be considered as a lead compound for the development of a new class of mPTP inhibitors and be used as mPTP de-sensitiser for basic research or clinical applications or emerge as a therapeutic application in mitochondria dysfunction-related disorders.
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spelling Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acidGallic acidmitochondriotropic antioxidantoxidative stressmitochondrial dysfunctionmitochondrial permeability transition poreAnimalsAntioxidantsCell SurvivalCells, CulturedDose-Response Relationship, DrugGallic AcidHep G2 CellsHumansMaleMitochondria, LiverMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMolecular StructureRatsRats, WistarStructure-Activity RelationshipDrug DiscoveryPharmacological interventions targeting mitochondria present several barriers for a complete efficacy. Therefore, a new mitochondriotropic antioxidant (AntiOxBEN3) based on the dietary antioxidant gallic acid was developed. AntiOxBEN3 accumulated several thousand-fold inside isolated rat liver mitochondria, without causing disruption of the oxidative phosphorylation apparatus, as seen by the unchanged respiratory control ratio, phosphorylation efficiency, and transmembrane electric potential. AntiOxBEN3 showed also limited toxicity on human hepatocarcinoma cells. Moreover, AntiOxBEN3 presented robust iron-chelation and antioxidant properties in both isolated liver mitochondria and cultured rat and human cell lines. Along with its low toxicity profile and high antioxidant activity, AntiOxBEN3 strongly inhibited the calcium-dependent mitochondrial permeability transition pore (mPTP) opening. From our data, AntiOxBEN3 can be considered as a lead compound for the development of a new class of mPTP inhibitors and be used as mPTP de-sensitiser for basic research or clinical applications or emerge as a therapeutic application in mitochondria dysfunction-related disorders.Taylor and Francis Ltd2018-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107712http://hdl.handle.net/10316/107712https://doi.org/10.1080/14756366.2018.1442831eng1475-63661475-6374Teixeira, JoséOliveira, CatarinaCagide, FernandoAmorim, RicardoGarrido, JorgeBorges, FernandaOliveira, Paulo J.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:RCAAP2023-07-28T09:20:34Zoai:estudogeral.uc.pt:10316/107712Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:24:01.974867Repositório 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 Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid
title Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid
spellingShingle Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid
Teixeira, José
Gallic acid
mitochondriotropic antioxidant
oxidative stress
mitochondrial dysfunction
mitochondrial permeability transition pore
Animals
Antioxidants
Cell Survival
Cells, Cultured
Dose-Response Relationship, Drug
Gallic Acid
Hep G2 Cells
Humans
Male
Mitochondria, Liver
Mitochondrial Membrane Transport Proteins
Mitochondrial Permeability Transition Pore
Molecular Structure
Rats
Rats, Wistar
Structure-Activity Relationship
Drug Discovery
title_short Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid
title_full Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid
title_fullStr Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid
title_full_unstemmed Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid
title_sort Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid
author Teixeira, José
author_facet Teixeira, José
Oliveira, Catarina
Cagide, Fernando
Amorim, Ricardo
Garrido, Jorge
Borges, Fernanda
Oliveira, Paulo J.
author_role author
author2 Oliveira, Catarina
Cagide, Fernando
Amorim, Ricardo
Garrido, Jorge
Borges, Fernanda
Oliveira, Paulo J.
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Teixeira, José
Oliveira, Catarina
Cagide, Fernando
Amorim, Ricardo
Garrido, Jorge
Borges, Fernanda
Oliveira, Paulo J.
dc.subject.por.fl_str_mv Gallic acid
mitochondriotropic antioxidant
oxidative stress
mitochondrial dysfunction
mitochondrial permeability transition pore
Animals
Antioxidants
Cell Survival
Cells, Cultured
Dose-Response Relationship, Drug
Gallic Acid
Hep G2 Cells
Humans
Male
Mitochondria, Liver
Mitochondrial Membrane Transport Proteins
Mitochondrial Permeability Transition Pore
Molecular Structure
Rats
Rats, Wistar
Structure-Activity Relationship
Drug Discovery
topic Gallic acid
mitochondriotropic antioxidant
oxidative stress
mitochondrial dysfunction
mitochondrial permeability transition pore
Animals
Antioxidants
Cell Survival
Cells, Cultured
Dose-Response Relationship, Drug
Gallic Acid
Hep G2 Cells
Humans
Male
Mitochondria, Liver
Mitochondrial Membrane Transport Proteins
Mitochondrial Permeability Transition Pore
Molecular Structure
Rats
Rats, Wistar
Structure-Activity Relationship
Drug Discovery
description Pharmacological interventions targeting mitochondria present several barriers for a complete efficacy. Therefore, a new mitochondriotropic antioxidant (AntiOxBEN3) based on the dietary antioxidant gallic acid was developed. AntiOxBEN3 accumulated several thousand-fold inside isolated rat liver mitochondria, without causing disruption of the oxidative phosphorylation apparatus, as seen by the unchanged respiratory control ratio, phosphorylation efficiency, and transmembrane electric potential. AntiOxBEN3 showed also limited toxicity on human hepatocarcinoma cells. Moreover, AntiOxBEN3 presented robust iron-chelation and antioxidant properties in both isolated liver mitochondria and cultured rat and human cell lines. Along with its low toxicity profile and high antioxidant activity, AntiOxBEN3 strongly inhibited the calcium-dependent mitochondrial permeability transition pore (mPTP) opening. From our data, AntiOxBEN3 can be considered as a lead compound for the development of a new class of mPTP inhibitors and be used as mPTP de-sensitiser for basic research or clinical applications or emerge as a therapeutic application in mitochondria dysfunction-related disorders.
publishDate 2018
dc.date.none.fl_str_mv 2018-12
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/10316/107712
http://hdl.handle.net/10316/107712
https://doi.org/10.1080/14756366.2018.1442831
url http://hdl.handle.net/10316/107712
https://doi.org/10.1080/14756366.2018.1442831
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1475-6366
1475-6374
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Taylor and Francis Ltd
publisher.none.fl_str_mv Taylor and Francis Ltd
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)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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