Conventional toxicological risk assessment methods mainly working on single chemicals that fail to adequately address the simultaneous exposure and their potential toxicity in humans. We herein investigated the toxic heavy metals lead (Pb), arsenic (As), and methylmercury (MeHg) and their binary mixtures role in neurodegenerative diseases. To characterize the toxicity of metal mixtures at the molecular level, we established a non-animal omics-based organ relevant cell model system. The obtained experimental data was refined by using the statistical and downstream functional analysis. The protein expression information substantiates the previous findings of single metal (Pb, As, and MeHg) induced alterations to mitochondrial dysfunction, oxidative stress, mRNA splicing, and ubiquitin system dysfunction relation to neurodegenerative diseases. The functional downstream analysis of single and binary mixtures protein data is presented in a comparative manner. The heavy metals mixtures' outcome showed significant differences in the protein expression compared to single metals that indicate metal mixtures exposure is more hazardous than single metal exposure. These results suggest that more comprehensive strategies are needed to improve the mixtures risk assessment in the future.

中文翻译：

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一种系统毒理学方法，用于比较重金属混合物（Pb，As，MeHg）对神经退行性疾病的影响。

常规毒理学风险评估方法主要针对无法充分解决同时暴露及其对人的潜在毒性的单一化学物质。我们在本文中研究了有毒重金属铅（Pb），砷（As）和甲基汞（MeHg）及其二元混合物在神经退行性疾病中的作用。为了在分子水平上表征金属混合物的毒性，我们建立了一个基于非动物组学的器官相关细胞模型系统。通过使用统计和下游功能分析来完善所获得的实验数据。蛋白质表达信息证实了先前单一金属（Pb，As和MeHg）诱导的线粒体功能障碍，氧化应激，mRNA剪接和泛素系统功能障碍与神经退行性疾病有关的改变。单一和二元混合物蛋白质数据的功能性下游分析以比较方式提供。重金属混合物的结果表明，与单一金属相比，蛋白质表达存在显着差异，这表明金属混合物暴露比单一金属暴露更具危害性。这些结果表明，将来需要更全面的策略来改进混合物风险评估。