Objective To explore the possible involvement of lysosomes in 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE 47) induced apoptosis in HepG2 cells.
Methods HepG2 cells were exposed to different levels of BDE 47 (0.00, 6.25, 12.50, 25.00, 50.00, 100.00 μmol/L) for 24 h, and the effects on cytotoxicity, reactive oxygen species (ROS), lysosomal and mitochondrial membrane stability were examined.
Results The data demonstrated that the 50.00 and 100.00 μmol/L BDE 47 statistically reduced cell viability (P< 0.01), compared with the control group. The BDE 47 exposure induced apoptosis in HepG2 cells significantly (P< 0.01) and in a dose-dependent manner (R2=0.981) and statistically increased ROS generation in HepG2 cells (P< 0.01, R2=0.918). The treatment with 12.50 μmol/L and higher doses of BDE 47 also led to elevated lysosomal membrane permeabilization (P< 0.05; P< 0.01) along with mitochondrial membrane potential disturbance (P< 0.01), both in a dose-effect manner (R2=0.918, R2=0.636, R2=0.678). The toxic effect of 50 μmol/L BDE 47 was significantly alleviated by 25 μmol/L CA-074 (P< 0.05), a specific inhibitor for cathepsin B, for which increased cell viability and decreased apoptosis were demonstrated.
Conclusion The findings indicate that the apoptotic event induced by BDE 47 in HepG2 might be initiated through a lysosomalmitochondrial pathway.
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