Exposure to decabromodiphenyl ether (BDE-209) produces mitochondrial dysfunction in rat liver and cell death

Author(s)

Pereira, Lilian C. ; Souza, Alecsandra O. ; Tasso, Maria J. ; Oliveira, Alana M. C. ; Duarte, Filipe V. ; Palmeira, Carlos M. ; Dorta, Daniel J.

• Document type: Journal article
• Source: JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES; v. 80, n. 19-21, p. 16-pg., 2017-01-01.

Abstract

Polybrominated diphenyl ethers (PBDE) are ubiquitous environmental pollutants. Exposure to these chemicals has been associated with developmental neurotoxicity, endocrine dysfunctions, reproductive disorders, and hepatotoxicity. The widespread use of PBDE as flame retardants has culminated in daily exposure of humans and wildlife to these contaminants and resulted in their banned use. Thus assessment of the potential effects of each PBDE congener on living organisms has become cause for concern. The aim of this study was to (1) examine the effects of decabromodiphenyl ether (BDE)-209 on different functions of HepG2 cells and (2) investigate whether this congener is involved in mitochondrial toxicity. The use of multiple methods was employed to (i) study the influence of BDE-209 on mitochondrial permeability transition (MPT) process in mitochondria isolated from rat liver and (ii) determine the consequential cellular damage. Our results showed that BDE-209 induced matrix swelling related to MPT with 10 mu M and ATP depletion with 0.1 mu M. In addition, 0.5 mu M BDE-209 reduced HepG2 cell viability, produced collapse of membrane potential, but increased levels of reactive oxygen species (ROS) after 48 h incubation. After 24 h with 5 mu M treatment elevated levels of ROS, DNA fragmentation and cytochrome c release, accompanied by caspase 9 and caspase 3 activation was noted. Taken together, these results suggest that short-duration exposure (24 or 48 h) to 0.5 mu M or 5 mu M BDE-209 concentrations diminished HepG2 cell viability due to apoptosis associated with mitochondrial dysfunction. (AU)

• FAPESP's process: 12/13123-0 - Evaluation of the effects of polybrominated diphenyl ethers congeners, BDE-100 and BDE-153, on the HepG2 cell line and human lymphocytes: cytotoxic, genotoxic and mutagenic effects.
• Grantee: Lilian Cristina Pereira
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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