Department of Occupational Health and Toxicology, School of Public Health, Nanchang University, Nanchang 330006, PR China; Jiangxi Province Key Laboratory of Preventive Medicine, Nanchang University, Nanchang 330006, PR China.
Department of Occupational Health and Toxicology, School of Public Health, Nanchang University, Nanchang 330006, PR China; Jiangxi Province Key Laboratory of Preventive Medicine, Nanchang University, Nanchang 330006, PR China.
Sci Total Environ. 2023 Oct 15;895:165009. doi: 10.1016/j.scitotenv.2023.165009. Epub 2023 Jun 21.
The heavy metals lead (Pb), cadmium (Cd), and mercury (Hg) that cause neurocognitive impairment have been extensively studied. These elements typically do not exist alone in the environment; they are often found with other heavy metals and can enter the body through various routes, thereby impacting health. Our previous research showed that low Pb, Cd, and Hg levels cause neurobehavioral impairments in weaning and adult rats. However, little is known about the biomarkers and mechanisms underlying Pb, Cd, and Hg mixture-induced neurological impairments. A combined analysis of metabolomic and proteomic data may reveal heavy metal-induced alterations in metabolic and protein profiles, thereby improving our understanding of the molecular mechanisms underlying heavy metal-induced neurological impairments. Therefore, brain tissue and serum samples were collected from rats exposed to a Pb, Cd, and Hg mixture for proteomic and metabolomic analyses, respectively. The analysis revealed 363 differential proteins in the brain and 206 metabolites in serum uniquely altered in the Pb, Cd, and Hg mixture exposure group, compared to those of the control group. The main metabolic impacted pathways were unsaturated fatty acids biosynthesis, linoleic acid metabolism, phenylalanine metabolism, and tryptophan metabolism. We further identified that the levels of arachidonic acid (C20:4 n-3) and, adrenic acid (C22:4 n-3) were elevated and that kynurenic acid (KA) and quinolinic acid (QA) levels and the KA/QA ratio, were decreased in the group exposed to the Pb, Cd, and Hg mixture. A joint analysis of the proteome and metabolome showed that significantly altered proteins such as LPCAT3, SLC7A11, ASCL4, and KYAT1 may participate in the neurological impairments induced by the heavy metal mixture. Overall, we hypothesize that the dysregulation of ferroptosis and kynurenine pathways is associated with neurological damage due to chronic exposure to a heavy metal mixture.
重金属铅（Pb）、镉（Cd）和汞（Hg）会导致神经认知障碍，这些元素已被广泛研究。这些元素在环境中通常不会单独存在，它们通常与其他重金属一起存在，并可以通过各种途径进入人体，从而影响健康。我们之前的研究表明，低水平的 Pb、Cd 和 Hg 会导致断奶和成年大鼠的神经行为障碍。然而，对于 Pb、Cd 和 Hg 混合物引起的神经损伤的生物标志物和机制知之甚少。代谢组学和蛋白质组学数据的联合分析可能揭示重金属诱导的代谢和蛋白质谱的改变，从而提高我们对重金属诱导的神经损伤的分子机制的理解。因此，分别从暴露于 Pb、Cd 和 Hg 混合物的大鼠中采集脑组织和血清样本，进行蛋白质组学和代谢组学分析。分析显示，与对照组相比，Pb、Cd 和 Hg 混合物暴露组的大脑中有 363 个差异蛋白，血清中有 206 个代谢物发生了独特改变。受影响的主要代谢途径是不饱和脂肪酸生物合成、亚油酸代谢、苯丙氨酸代谢和色氨酸代谢。我们进一步发现，花生四烯酸（C20:4 n-3）和二十二碳四烯酸（C22:4 n-3）的水平升高，而犬尿氨酸（KA）和喹啉酸（QA）的水平以及 KA/QA 比值降低，在 Pb、Cd 和 Hg 混合物暴露组中。蛋白质组和代谢组的联合分析表明，LPCAT3、SLC7A11、ASCL4 和 KYAT1 等显著改变的蛋白质可能参与了重金属混合物引起的神经损伤。总的来说，我们假设铁死亡和犬尿氨酸途径的失调与慢性暴露于重金属混合物引起的神经损伤有关。
