Cytotoxicity of hexabromocyclododecane, 1,2-dibromo-4-(1,2-dibromoethyl) cyclohexane and 1,2,5,6-tetrabromocyclooctane in human SH-SY5Y neuroblastoma cells
2020
Shi, Xiaoli | Wen, Bei | Huang, Honglin | Zhang, Shuzhen
With the listing of the of cycloaliphatic brominated flame retardants (CBFR) hexabromocyclododecane (HBCD) as a persistent organic pollutant (POP) by the Stockholm Convention, much attention has been paid to the environmental behaviors and biological effects of HBCD, as well as its potential alternatives, such as 1,2-dibromo-4-(1,2-dibromoethyl) cyclohexane (TBECH) and 1,2,5,6-tetrabromocyclooctane (TBCO). In this study, the neurotoxicity of HBCD, TBECH, and TBCO in human SH-SY5Y cells were compared. The results showed that HBCD, TBECH, and TBCO induced cytotoxicity, including dose–dependent cell viability decreases, cell membrane permeability increases, cytoskeleton development damage, and apoptosis induction, with the cytotoxicity in the order of HBCD > TBCO > TBECH. The expression levels of apoptotic proteins (caspase-3, Bax, caspase-9, Bcl-2, and cytochrome c (Cyt c)) followed the same order, which indicated that mitochondrial apoptotic pathway may be one of the mechanisms responsible for their neurotoxicity. In order to study the mechanisms of cytotoxicity, CBFRs-induced reactive oxygen species (ROS) and the intracellular calcium levels were determined. The ROS levels were significantly elevated for three CBFRs treatment, suggesting that oxidative stress contributes to their cytotoxicity. The intracellular calcium concentrations were significantly enhanced for HBCD and TBCO treatment, but not for TBECH, indicating that in addition to ROS, cytotoxicity of HBCD and TBCO may follow Ca²⁺-mediated apoptotic pathway. This study first compared the neurotoxicity of different CBFRs, providing valuable information for their risk assessment.
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