Previous studies on copper pyrithione (CPT) and zinc pyrithione (ZPT) as antifouling agents have mainly focused on marine organisms. Even though CPT and ZPT pose a risk of human exposure, their neurotoxic effects remain to be elucidated. Therefore, in this study, the cytotoxicity and neurotoxicity of CPT and ZPT were evaluated after the exposure of human SH-SY5Y/astrocytic co-cultured cells to them. The results showed that, in a co-culture model, CPT and ZPT induced cytotoxicity in a dose-dependent manner (~ 400 nM). Exposure to CPT and ZPT suppressed all parameters in the neurite outgrowth assays, including neurite length. In particular, exposure led to neurotoxicity at concentrations with low or no cytotoxicity (~ 200 nM). It also downregulated the expression of genes involved in neurodevelopment and maturation and upregulated astrocyte markers. Moreover, CPT and ZPT induced mitochondrial dysfunction and promoted the generation of reactive oxygen species. Notably, N-acetylcysteine treatment showed neuroprotective effects against CPT- and ZPT-mediated toxicity. We concluded that oxidative stress was the major mechanism underlying CPT- and ZPT-induced toxicity in the co-cultured cells.

以往关于吡啶硫酮铜（CPT）和吡啶硫酮锌（ZPT）作为防污剂的研究主要集中在海洋生物。尽管 CPT 和 ZPT 存在人类暴露的风险，但它们的神经毒性作用仍有待阐明。因此，在本研究中，在人SH-SY5Y/星形胶质细胞共培养细胞暴露于CPT和ZPT后，评估了它们的细胞毒性和神经毒性。结果表明，在共培养模型中，CPT 和 ZPT 以剂量依赖性方式（约 400 nM）诱导细胞毒性。暴露于 CPT 和 ZPT 抑制了神经突生长测定中的所有参数，包括神经突长度。特别是，在低细胞毒性或无细胞毒性（约 200 nM）的浓度下，暴露会导致神经毒性。它还下调了涉及神经发育和成熟的基因的表达，并上调了星形胶质细胞标记物。此外，CPT和ZPT诱导线粒体功能障碍并促进活性氧的产生。值得注意的是， N-乙酰半胱氨酸治疗显示出针对 CPT 和 ZPT 介导的毒性的神经保护作用。我们得出结论，氧化应激是共培养细胞中 CPT 和 ZPT 诱导毒性的主要机制。