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

Author(s)

Pereira, Lilian Cristina ^{[1, 2, 3]} ; Cabral Miranda, Luiz Felipe ^[4] ; Franco-Bernardes, Mariana Furio ^[1] ; Tasso, Maria Julia ^[4] ; Duarte, Filipe Valente ^{[5, 6]} ; Inacio Varela, Ana Teresa ^{[5, 6]} ; Rolo, Anabela Pinto ^{[5, 6]} ; Marques Palmeira, Carlos Manuel ^{[5, 6]} ; Dorta, Daniel Junqueira ^{[4, 7]}

Affiliation

^[1] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Clin Toxicol & Bromatol Anal, Ribeirao Preto - Brazil

^[2] Sao Paulo State Univ, Fac Agron Sci Botucatu, Dept Bioproc & Biotechnol, Botucatu, SP - Brazil

^[3] Sao Paulo State Univ, Botucatu Med Sch, Dept Pathol, Ctr Evaluat Environm Impact Human Hlth TOXICAM, Botucatu, SP - Brazil

^[4] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, Ribeirao Preto - Brazil

^[5] Univ Coimbra, Dept Life Sci, Coimbra - Portugal

^[6] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra - Portugal

^[7] UNESP, INCT DATREM, Natl Inst Alternat Technol Detect Toxicol Evaluat, Inst Chem, POB 355, BR-14800900 Araraquara, SP - Brazil

• Document type: Journal article
• Source: Chemico-Biological Interactions; v. 291, p. 192-201, AUG 1 2018.
• Web of Science Citations: 3

Abstract

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 mu M. 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 MIT 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. (AU)

• FAPESP's process: 09/06912-6 - Assessment of mitochondrial and cellular changes induced by representatives of major classes of poly-brominated biphenyls (PBDEs)
• Grantee: Daniel Junqueira Dorta
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 10/02661-6 - Assessment of mitochondrial alterations induced by representatives of major classes of poly-brominated biphenyls (PBDEs)
• Grantee: Lilian Cristina Pereira
• Support Opportunities: Scholarships in Brazil - Master