Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/11641
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dc.contributor.authorRolo, Anabela P.-
dc.contributor.authorOliveira, Paulo J.-
dc.contributor.authorMoreno, António J. M.-
dc.contributor.authorPalmeira, Carlos M.-
dc.date.accessioned2009-10-09T12:48:28Z-
dc.date.available2009-10-09T12:48:28Z-
dc.date.issued2000-09-
dc.identifier.citationToxicological Sciences. 57:1 (2000) 177-185en_US
dc.identifier.issn1096-6080-
dc.identifier.urihttps://hdl.handle.net/10316/11641-
dc.description.abstractIt has been pointed out that intracellular accumulation of bile acids cause hepatocyte injury in cholestatic disease process. This study was aimed to test if cytotoxicity of these compounds is mediated through mitochondria dysfunction. Bile acids effects on isolated rat liver mitochondrial were analyzed by monitoring changes in membrane potential and mitochondrial respiration, as well as alterations in H+ membrane permeability and mitochondrial permeability transition pore induction. Increasing concentrations of the bile acids litocholic (LCA), deoxycholic (DCA), ursodeoxycholic (UDCA), chenodeoxycholic (CDCA), glycochenodeoxycholic (GCDC), or taurochenodeoxycholic (TCDC) decrease transmembrane potential ({Delta}{Psi}) developed upon succinate energization. These compounds also decreased state 3 respiration and enhanced state 4. We have also demonstrated that the observed concentration-dependent stimulation of state 4 by LCA, DCA, CDCA, TCDC, and GCDC, is associated with an enhanced permeability of mitochondria to H+. Addition of LCA, DCA, CDCA, TCDC, GCDC, and UDCA to mitochondria energized with succinate resulted in a dose-dependent membrane depolarization and stimulation of mitochondrial permeability transition. Tauroursodeoxycholate (TUDC) elicited no significant effect on succinate-supported mitochondrial bioenergetics. In contrast, in the presence of glycoursodeoxycholic (GUDC), {Delta}{Psi} increases as a function of bile salt concentration. The results of this investigation demonstrate that at toxicologically relevant concentrations, most but not all bile acids alter mitochondrial bioenergetics, so impairment of mitochondrial function can be clinically relevant for patients with cholestasis.en_US
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.rightsopenAccessen_US
dc.subjectMitochondriaen_US
dc.subjectBile acidsen_US
dc.subjectPermeability transition poreen_US
dc.subjectMembrane potentialen_US
dc.subjectRespirationen_US
dc.titleBile acids affect liver mitochondrial bioenergetics: possible relevance for cholestasis therapyen_US
dc.typearticleen_US
uc.controloAutoridadeSim-
item.openairetypearticle-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.grantfulltextopen-
item.fulltextCom Texto completo-
crisitem.author.deptFaculty of Sciences and Technology-
crisitem.author.parentdeptUniversity of Coimbra-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitMARE - Marine and Environmental Sciences Centre-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0003-3535-9630-
crisitem.author.orcid0000-0002-5201-9948-
crisitem.author.orcid0000-0003-3575-7604-
crisitem.author.orcid0000-0002-2639-7697-
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais
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