Decabromodiphenyl ether initiates mitochondria-dependent apoptosis by disrupting calcium homeostasis in mice livers

Decabromodiphenyl ether (BDE-209) tends to accumulate in lipid-rich tissues and targets the liver since its high lipophilicity. This study aimed to investigate the effects of BDE-209 on mouse liver and reveal the underlying toxicological mechanisms. Here we firstly confirmed that treatment of BDE-209 could lead to an imbalance of redox and promote apoptosis with a mitochondria-dependent manner in mice livers. Next, the transmission electron microscope (TEM) image revealed BDE-209 induced changes in mitochondrial morphology and increased endoplasmic reticulum (ER) - mitochondrial contact. ER stress was involved in the apoptosis process, which was displayed by the enhancive ER stress makers . Finally, from the increased abundance of cellular pivotal Ca2+ signals transducer CaM, activating Ca2+ release channel Sig-1R and IP3R1, and the stronger fluorescence density of mitochondria-specifically Ca2+ labeled probe Rhod-2 in vitro, we summarized that there was overloaded mitochondrial Ca2+ in hepatocytes of BDE-209 treated mice. In conclusion, these results partly illustrated evidence to reveal a potential mechanism of BDE-209-induced hepatoxicity, where oxidative stress-induced-ER stress led to the over-release of Ca2+, followed by the overloaded mitochondrial Ca2+, and cell apoptosis initiated. Our findings provided a theoretical basis for further studying.