DBDPE and ZnO NPs synergistically induce neurotoxicity of SK-N-SH cells and activate mitochondrial apoptosis signaling pathway and Nrf2-mediated antioxidant pathway

Decabromodiphenyl ethane (DBDPE), a new brominated flame retardant, could negatively affect neurobehavior and pose health risks to humans. Humans are also exposed to widely used nanomaterials. This study investigated the combined toxic effects and action types of DBDPE and Zinc oxide nanoparticles (ZnO NPs) on human neu-roblastoma SK-N-SH cells and the toxicity mechanisms. DBDPE inhibited the viability of SK-N-SH cells by 21.87% at 25 mg/L. ZnO NPs synergistically exacerbated the toxic effects of DBDPE. DBDPE and ZnO NPs caused excessive ROS production and inhibition of antioxidant enzyme (SOD and GSH) activity in cells, thus causing oxidative cellular damage. Moreover, DBDPE and ZnO NPs caused apoptosis by disrupting mitochondrial kinetic homeostasis, reducing mitochondrial membrane potential (MMP), increasing cytochrome C release and regu-lating Bax/Bcl-2 and Caspase-3 mRNA and protein expression. DBDPE and ZnO NPs increased the mRNA expression of nuclear factor erythroid 2-related factor (Nrf2) and its downstream genes. The molecular mech-anisms revealed that oxidative stress, apoptosis and mitochondrial dysfunction were the critical factors in combined cytotoxicity. The bioinformatics analysis further indicated that co-exposure affected Nrf2 activation, apoptotic factors expression and mitochondrial fusion. The findings enrich the risk perception of neurotoxicity caused by DBDPE and ZnO NPs.

Automated summary

The combined effects of Decabromodiphenyl ethane (DBDPE) and Zinc oxide nanoparticles (ZnO NPs) on human neuroblastoma SK-N-SH cells were investigated in this study. The results showed that the two substances acted synergistically to exert toxic effects, causing excessive ROS production, inhibition of antioxidant enzyme activity, disruption of mitochondrial kinetic homeostasis, and apoptosis through regulation of related genes and proteins. The findings highlight the risk of neurotoxicity associated with DBDPE and ZnO NPs exposure.