Liao Qilong, Huang Lulu, Cai Fengshan, Luo Weikeng, Li Min, Yang Juanjuan, Tang Bin, Xiao Xinyi, Yan Xiao, Zheng Jing
State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, Research Center of Emerging Contaminants, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510655, PR China; Guangdong-Hong Kong-Macao Joint Laboratory for Environmental Pollution and Control, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, PR China.
State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, Research Center of Emerging Contaminants, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510655, PR China; The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang 550025, PR China.
Sci Total Environ. 2024 Apr 15;921:170975. doi: 10.1016/j.scitotenv.2024.170975. Epub 2024 Feb 13.
Studies on the dose effects of kidney impairment and metabolomes in co-exposure to polycyclic aromatic hydrocarbons (PAHs) and metals are limited. We aimed to identify overall associations and metabolic perturbations in 130 participants (53 petrochemical workers and 77 controls) exposed to a PAHs-metals mixture in Southern China. The urinary 7 hydroxylated PAHs and 15 metal(loid)s were determined, and serum creatinine, beta-2 microglobulin, and estimated glomerular filtration rate were health outcomes. The liquid chromatography-mass spectrometry-based method was applied to serum metabolomics. Generalized weighted quantile sum (gWQS) regressions were used to estimate the overall dose-response relationships, and pathway analysis, "meet-in-the-middle" approach, and mediation effect analyses were conducted to identify potential metabolites and biological mechanisms linking exposure with nephrotoxic effects. Our results indicated that renal function reduction was associated with a PAHs-metals mixture in a dose-dependent manner, and 1-hydroxynaphthalene and copper were the most predominant contributors among the two families of pollutants. Furthermore, the metabolic disruptions associated with the early onset of kidney impairment induced by the combination of PAHs and metals encompassed pathways such as phenylalanine-tyrosine-tryptophan biosynthesis, phenylalanine metabolism, and alpha-linolenic acid metabolism. In addition, the specifically identified metabolites demonstrated excellent potential as bridging biomarkers connecting the reduction in renal function with the mixture of PAHs and metals. These findings shed light on understanding the overall associations and metabolic mechanism of nephrotoxic effects of co-exposure to PAHs and metals.
关于多环芳烃（PAHs）和金属共同暴露对肾功能损害及代谢组影响的剂量效应研究有限。我们旨在确定中国南方130名暴露于PAHs-金属混合物的参与者（53名石化工人和77名对照）的总体关联及代谢扰动情况。测定了尿中7种羟基化PAHs和15种金属（类金属），并将血清肌酐、β2微球蛋白和估计肾小球滤过率作为健康指标。采用基于液相色谱-质谱联用的方法进行血清代谢组学分析。使用广义加权分位数和（gWQS）回归估计总体剂量反应关系，并进行通路分析、“中间相遇”方法和中介效应分析，以确定潜在的代谢物以及将暴露与肾毒性效应联系起来的生物学机制。我们的结果表明，肾功能降低与PAHs-金属混合物呈剂量依赖性相关，1-羟基萘和铜是这两类污染物中最主要的贡献因素。此外，PAHs和金属联合诱导肾功能损害早期发生相关的代谢紊乱包括苯丙氨酸-酪氨酸-色氨酸生物合成、苯丙氨酸代谢和α-亚麻酸代谢等通路。此外，特异性鉴定出的代谢物作为连接肾功能降低与PAHs和金属混合物的桥梁生物标志物具有极佳的潜力。这些发现有助于理解PAHs和金属共同暴露肾毒性效应的总体关联及代谢机制。
