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

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 µM and ATP depletion with 0.1 µM. In addition, 0.5 μM 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 μM 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 μM or 5 μM BDE-209 concentrations diminished HepG2 cell viability due to apoptosis associated with mitochondrial dysfunction.

Chemical, structural, and ultrastructural analysis of waste from the carrageenan and sugar-bioethanol processes for future bioenergy generation

“…Although our previous results have shown autophagic induction [39,40], persistent mitochondrial damage may have led these cells to death by apoptosis elicited by different stimuli, to culminate in phosphatidylserine exposure and nuclear condensation and fragmentation. Anthropogenic chemicals and other stressors can impact macromolecular mitochondrial structures via molecular interference or mechanical damage [22].…”

“…We have recently published that BDE-153 and other congeners can cause genomic instability, as revealed by comet assay results obtained after exposure to BDE-153 at 5, 10, or 25 μM for only 4 h [38]. In addition, we have shown the same compound can induce HepG2 cell autophagy [39,40] in an attempt to save cells from the damage caused by BDE-153. Autophagy is a pro-survival process that occurs under stressful conditions, such as xenobiotics impact [29].…”

Evaluation of the phytotoxicity of decabromodiphenyl ether (BDE-209) in Chinese cabbage

“…According to previous studies, BDE-209 exhibits toxicity to plants and animals, posing emerging risks to humans and ecosystems via the food chain (Hu et al 2010, Ji et al 2017, Pereira et al 2017, Li et al 2018. PBDEs have been detected in human tissues (Cai et al 2015).…”

Hepatic oxidative stress, DNA damage and apoptosis in adult zebrafish following sub‐chronic exposure to BDE‐47 and BDE‐153

“…The induced effects of xenobiotics related to DNA damage and apoptosis have been well investigated by in vitro or ex vivo studies. For example, previous studies indicated that different PBDE congeners including BDE‐47 and BDE‐153 induced mitochondrial damage, genetoxicity, and apoptosis in rat liver and HepG2 cells 25‐29 . However, in vivo studies, the DNA damage and apoptosis induced by PBDEs still need to be further explored.…”

“…For example, previous studies indicated that different PBDE congeners including BDE-47 and BDE-153 induced mitochondrial damage, genetoxicity, and apoptosis in rat liver and HepG2 cells. [25][26][27][28][29] However, in vivo studies, the DNA damage and apoptosis induced by PBDEs still need to be further explored.…”