Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/25792
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dc.contributor.authorSilva, Filomena S. G.-
dc.contributor.authorRibeiro, Mariana P. C.-
dc.contributor.authorSantos, M. S.-
dc.contributor.authorRocha-Pereira, Petronila-
dc.contributor.authorSantos-Silva, Alice-
dc.contributor.authorCustódio, José B. A.-
dc.date.accessioned2014-05-28T10:22:17Z-
dc.date.available2014-05-28T10:22:17Z-
dc.date.issued2013-
dc.identifier.urihttps://hdl.handle.net/10316/25792-
dc.description.abstractThe combination of isotretinoin (13-cis-retinoic acid) with antiestrogens seems to be a promising strategy for cancer chemotherapy. The aim of the study was to evaluate the effects of isotretinoin alone or in combination with 4-hydroxytamoxifen (OHTAM) and with its prodrug tamoxifen (TAM), on the functions of rat liver mitochondria, i.e., mitochondrial permeability transition (MPT), bioenergetic functions and adenine nucleotide translocase (ANT). Isotretinoin (5 nmol/mg protein) induced the Ca2+-dependent MPT pore opening in mitochondria energized with succinate, which was prevented by OHTAM, cyclosporine A, TAM and ANT ligands. When mitochondria were energized with glutamate/malate and in the absence of added Ca2+ isotretinoin decreased the state 3 respiration, the ATP levels, the active ANT content and increased the lag phase of the phosphorylation cycle, demonstrating that isotretinoin decreased the mitochondrial phosphorylation efficiency. These changes of isotretinoin in bioenergetic parameters were not significant in the presence of succinate. The effects of isotretinoin at 5 nmol/mg protein on the Ca2+-dependent MPT and phosphorylative efficacy may be related with interactions with the ANT. Above 10 nmol/mg protein isotretinoin strongly diminished the active ANT content, decreased the Δψ, inhibited the complex I and induced proton leak through the Fo fraction of complex V. The combination of OHTAM with isotretinoin only induced significant changes in the energy production systems at concentrations ≥5 nmol isotretinoin/mg protein. Therefore, our results suggest that isotretinoin-associated liver toxicity is possibly related with mitochondrial dysfunctions and that the combination with OHTAM may contribute to decrease its toxicity.por
dc.description.sponsorshipThis study was supported by PhD grant (SFRH/ BD/37686/2007) attributed to F.S.G. Silva by Fundação para a Ciência e Tecnologia.por
dc.language.isoengpor
dc.publisherSpringer Sciencepor
dc.rightsopenAccesspor
dc.subjectIsotretinoinpor
dc.subject4-hydroxytamoxifenpor
dc.subjectTamoxifenpor
dc.subjectOxidative phosphorylation systempor
dc.subjectMitochondrial permeability transitionpor
dc.titleThe antiestrogen 4-hydroxytamoxifen protects against isotretinoin-induced permeability transition and bioenergetic dysfunction of liver mitochondria: comparison with tamoxifenpor
dc.typearticlepor
degois.publication.firstPage383por
degois.publication.lastPage396por
degois.publication.issue4por
degois.publication.titleJournal of Bioenergetics and Biomembranespor
dc.relation.publisherversionhttp://link.springer.com/article/10.1007%2Fs10863-013-9517-9por
dc.peerreviewedYespor
dc.identifier.doi10.1007/s10863-013-9517-9-
degois.publication.volume45por
item.openairetypearticle-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.grantfulltextopen-
item.fulltextCom Texto completo-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0002-6881-9392-
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais
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J Bioenerg Biomembr (2013) 45, 383–396.pdf601.12 kBAdobe PDFView/Open
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