Mitochondrial damage and apoptosis: Key features in BDE-153-induced hepatotoxicity

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dc.contributor.authorPereira, Lilian Cristina [UNESP]
dc.contributor.authorCabral Miranda, Luiz Felipe
dc.contributor.authorFranco-Bernardes, Mariana Furio
dc.contributor.authorTasso, Maria Julia
dc.contributor.authorDuarte, Filipe Valente
dc.contributor.authorInácio Varela, Ana Teresa
dc.contributor.authorRolo, Anabela Pinto
dc.contributor.authorMarques Palmeira, Carlos Manuel
dc.contributor.authorDorta, Daniel Junqueira [UNESP]
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversity of Coimbra
dc.date.accessioned2018-12-11T17:21:03Z
dc.date.available2018-12-11T17:21:03Z
dc.date.issued2018-08-01
dc.description.abstractBrominated flame retardants are used in consumer goods to increase product resistance to fire and/or high temperatures. Polybrominated diphenyl ethers (PBDEs) are the most commonly employed class of brominated flame retardants because they are inexpensive and can effectively prevent flame from spreading. PBDEs are persistent, can bioaccumulate, are transported over long distances, and display toxicity. However, their toxic mechanisms of action have not been well established. Because mitochondria are recognized as the main energy-producing cell organelle and play a vital role in cellular function maintenance, here we apply mitochondria as an experimental model to evaluate the toxic effects of the PBDE congener BDE-153 (Hexa-BDE) at concentrations ranging from 0.1 to 25 μM. We also assess BDE-153 cytotoxicity to HepG2 cells in order to elucidate its mechanisms of toxicity. Exposure to BDE-153 affects isolated mitochondria: this congener can interact with the mitochondrial membrane, to dissipate the membrane potential and to induce significant ATP depletion. Furthermore, BDE-153 can diminish MTT reduction and cell proliferation and can interfere in cell cycle, as evaluated in cell cultures. These cytotoxic effects are related to mitochondrial dysfunction due to mitochondrial membrane potential dissipation and reactive oxygen species accumulation. These effects result in apoptotic cell death, as demonstrated by phosphatidylserine maintenance on the cell membrane external surface, nuclear condensation and fragmentation, and presence of pro-apoptotic factors such as cytochrome c and Apoptosis-inducing Factor (AIF) plus caspase 3 activation in the cytosol. Together, our results show PBDEs can induce cytotoxicity, reinforcing the idea that these compounds pose a risk to the exposed population.en
dc.description.affiliationDepartment of Clinical Toxicological and Bromatological Analysis Faculty of Pharmaceutical Sciences of Ribeirão Preto University of São Paulo
dc.description.affiliationDepartment of Bioprocesses and Biotechnology Faculty of Agronomic Sciences of Botucatu São Paulo State University
dc.description.affiliationDepartment of Pathology São Paulo State University Botucatu Medical School Center for the Evaluation of the Environmental Impact on Human Health (TOXICAM)
dc.description.affiliationDepartamento de Química Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Universidade de São Paulo
dc.description.affiliationDepartment of Life Sciences University of Coimbra and Center for Neurosciences and Cell Biology University of Coimbra
dc.description.affiliationNational Institute for Alternative Technologies of Detection Toxicological Evaluation and Removal of Micropollutants and Radioactives (INCT-DATREM) Unesp Institute of Chemistry, P.O. Box 355
dc.description.affiliationUnespDepartment of Bioprocesses and Biotechnology Faculty of Agronomic Sciences of Botucatu São Paulo State University
dc.description.affiliationUnespDepartment of Pathology São Paulo State University Botucatu Medical School Center for the Evaluation of the Environmental Impact on Human Health (TOXICAM)
dc.description.affiliationUnespNational Institute for Alternative Technologies of Detection Toxicological Evaluation and Removal of Micropollutants and Radioactives (INCT-DATREM) Unesp Institute of Chemistry, P.O. Box 355
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipUniversidade de São Paulo
dc.description.sponsorshipIdCAPES: PVE-A018/2012
dc.format.extent192-201
dc.identifierhttp://dx.doi.org/10.1016/j.cbi.2018.06.021
dc.identifier.citationChemico-Biological Interactions, v. 291, p. 192-201.
dc.identifier.doi10.1016/j.cbi.2018.06.021
dc.identifier.issn1872-7786
dc.identifier.issn0009-2797
dc.identifier.scopus2-s2.0-85049064624
dc.identifier.urihttp://hdl.handle.net/11449/176502
dc.language.isoeng
dc.relation.ispartofChemico-Biological Interactions
dc.relation.ispartofsjr1,033
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.titleMitochondrial damage and apoptosis: Key features in BDE-153-induced hepatotoxicityen
dc.typeArtigo
unesp.author.orcid0000-0003-0024-7655 0000-0003-0024-7655 0000-0003-0024-7655[1]
unesp.author.orcid0000-0002-2183-0412[3]
unesp.author.orcid0000-0003-0287-0328[5]
unesp.author.orcid0000-0002-8822-4935 0000-0002-8822-4935[9]

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