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

• Published in: Journal of hazardous materials 2023-01, Vol.441, p.129872-129872, Article 129872
• Main Authors: Dong, Liying, Wang, Shutao, Zhang, Lin, Liu, Dongmei, You, Hong
• Format: Article
• Language: English
• Subjects: Apoptosis; DBDPE and ZnO NPs; Mitochondrial function disorders; Neurotoxicity; Nrf2 pathway; SK-N-SH cells
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2022.129872

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 neuroblastoma 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 regulating 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 mechanisms 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. [Display omitted] •DBDPE and ZnO NPs synergistically induce neurotoxicity in SK-N-SH cells.•DBDPE and ZnO NPs induce apoptosis through the intracellular mitochondrial pathway.•Excess ROS is a driver of apoptosis in SK-N-SH cells.•The Nrf2 antioxidant defense pathway is activated in SK-N-SH cells when exposed to DBDPE and ZnO NPs.