Many studies have focused on the neurotoxic effects of single metals, while investigation on the exposure to metal mixtures, which mainly occur in real‐life situations, is scarce. This study sought to assess the neurotoxic effect of Ni, Co, and Pb binary mixtures and their individual effects in hippocampal neuronal cells (HT‐22). Cells were exposed to Ni, Co, and Pb separately for 48 h at 37°C and 5% CO2, and cell viability was assessed. Morphological assessment of the cells exposed to binary mixtures of Co, Ni, and Pb and single metals was assessed using a microscope. Furthermore, acetylcholinesterase (AChE) activity, oxidative stress biomarkers (glutathione [GSH] and malondialdehyde [MDA] levels, catalase [CAT], and glutathione‐S transferase [GST] activities) and nitric oxide [NO] levels were evaluated after treatment with the binary mixtures and single metals. Binary mixtures of the metals reduced cell viability, exerting an additivity action. The combinations also exerted synergistic action, as revealed by the combination index. Furthermore, a significant reduction in AChE activity, GSH levels, CAT and GST activities, and high MDA and NO levels were observed in neuronal cells. The additive interactions and synergistic actions of the binary mixtures might contribute to the significant reduction of AChE activity, GSH levels, GST, and CAT activities, and an increase in MDA and NO levels. The findings from this study revealed significant evidence that binary mixtures of Co, Pb, and Ni may induce impaired neuronal function and, ultimately, neurodegeneration.

中文翻译：

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海马神经元细胞中钴、镍和铅的个体和二元混合物的神经毒性机制评估


许多研究都集中在单一金属的神经毒性作用上，而对主要发生在现实生活中的金属混合物的暴露的研究却很少。本研究旨在评估 Ni、Co 和 Pb 二元混合物的神经毒性作用及其对海马神经元细胞 （HT-22） 的个体影响。将细胞在 37°C 和 5% CO2 下分别暴露于 Ni、Co 和 Pb 48 h，并评估细胞活力。使用显微镜评估暴露于 Co、Ni 和 Pb 的二元混合物以及单一金属的细胞的形态学评估。此外，乙酰胆碱酯酶 （AChE） 活性、氧化应激生物标志物 （谷胱甘肽 [GSH] 和丙二醛 [MDA] 水平、过氧化氢酶 [CAT] 和谷胱甘肽-S 转移酶 [GST] 活性）和一氧化氮 [NO] 水平在用二元混合物和单一金属处理后进行评估。金属的二元混合物降低了细胞活力，发挥了加性作用。这些组合还发挥了协同作用，如组合指数所示。此外，在神经元细胞中观察到 AChE 活性、 GSH 水平、 CAT 和 GST 活性以及高 MDA 和 NO 水平显着降低。二元混合物的加性相互作用和协同作用可能有助于 AChE 活性、 GSH 水平、GST 和 CAT 活性的显著降低，以及 MDA 和 NO 水平的增加。这项研究的结果揭示了重要的证据表明，Co、Pb 和 Ni 的二元混合物可能会诱导神经元功能受损，并最终导致神经退化。