Mitochondrial damage and apoptosis: Key features in BDE-153-induced hepatotoxicity
Autor: | Filipe V. Duarte, Lilian Cristina Pereira, Mariana Furio Franco-Bernardes, Daniel Junqueira Dorta, Ana T. Varela, Maria Júlia Tasso, Luiz Felipe Cabral Miranda, Carlos M. Palmeira, Anabela P. Rolo |
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Přispěvatelé: | Universidade de São Paulo (USP), Universidade Estadual Paulista (Unesp), University of Coimbra |
Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Polybrominated Biphenyls Apoptosis Mitochondria Liver Phosphatidylserines Mitochondrion Toxicology Oxidative Phosphorylation 03 medical and health sciences Adenosine Triphosphate Polybrominated diphenyl ethers Animals Humans Rats Wistar Fragmentation (cell biology) Inner mitochondrial membrane Membrane Potential Mitochondrial biology Cell growth Chemistry Cytochrome c Hep G2 Cells General Medicine Cell biology Cytosol 030104 developmental biology Liver Mitochondrial Membranes CÉLULAS MORTAS biology.protein Calcium Mitochondrial Swelling Reactive Oxygen Species |
Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
ISSN: | 0009-2797 |
DOI: | 10.1016/j.cbi.2018.06.021 |
Popis: | Made available in DSpace on 2018-12-11T17:21:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-08-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Universidade de São Paulo Brominated 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. Department of Clinical Toxicological and Bromatological Analysis Faculty of Pharmaceutical Sciences of Ribeirão Preto University of São Paulo Department of Bioprocesses and Biotechnology Faculty of Agronomic Sciences of Botucatu São Paulo State University Department of Pathology São Paulo State University Botucatu Medical School Center for the Evaluation of the Environmental Impact on Human Health (TOXICAM) Departamento de Química Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Universidade de São Paulo Department of Life Sciences University of Coimbra and Center for Neurosciences and Cell Biology University of Coimbra National Institute for Alternative Technologies of Detection Toxicological Evaluation and Removal of Micropollutants and Radioactives (INCT-DATREM) Unesp Institute of Chemistry, P.O. Box 355 Department of Bioprocesses and Biotechnology Faculty of Agronomic Sciences of Botucatu São Paulo State University Department of Pathology São Paulo State University Botucatu Medical School Center for the Evaluation of the Environmental Impact on Human Health (TOXICAM) National Institute for Alternative Technologies of Detection Toxicological Evaluation and Removal of Micropollutants and Radioactives (INCT-DATREM) Unesp Institute of Chemistry, P.O. Box 355 CAPES: PVE-A018/2012 |
Databáze: | OpenAIRE |
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