Graduate Institute of Medicine, College of Medicine, Kaohsiung Medicine University, Kaohsiung City 807, Taiwan.
Department of Public Health and Environmental Medicine, College of Medicine, Kaohsiung Medicine University, Kaohsiung City 807, Taiwan.
Int J Environ Res Public Health. 2022 Jun 16;19(12):7399. doi: 10.3390/ijerph19127399.
Exposure to heavy metals could lead to adverse health effects by oxidative reactions or inflammation. Some essential elements are known as reactors of anti-inflammatory enzymes or coenzymes. The relationship between tumor necrosis factor alpha (TNF-α) and heavy metal exposures was reported. However, the interaction between toxic metals and essential elements in the inflammatory response remains unclear. This study aimed to explore the association between arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), copper (Cu), selenium (Se), and zinc (Zn) in blood and TNF-α as well as kidney function. We enrolled 421 workers and measured the levels of these seven metals/metalloids and TNF-α in blood; kidney function was calculated by CKD-EPI equation. We applied weighted quantile sum (WQS) regression and group WQS regression to assess the effects of metal/metalloid mixtures to TNF-α and kidney function. We also approached the relationship between metals/metalloids and TNF-α by generalized additive models (GAM). The relationship of the exposure−response curve between Pb level and TNF-α in serum was found significantly non-linear after adjusting covariates (p < 0.001). Within the multiple-metal model, Pb, As, and Zn were associated with increased TNF-α levels with effects dedicated to the mixture of 50%, 31%, and 15%, respectively. Grouped WQS revealed that the essential metal group showed a significantly negative association with TNF-α and kidney function. The toxic metal group found significantly positive associations with TNF-α, serum creatinine, and WBC but not for eGFR. These results suggested Pb, As, Zn, Se, and mixtures may act on TNF-α even through interactive mechanisms. Our findings offer insights into what primary components of metal mixtures affect inflammation and kidney function during co-exposure to metals; however, the mechanisms still need further research.
重金属暴露可通过氧化反应或炎症导致不良健康影响。一些必需元素被认为是抗炎酶或辅酶的反应剂。已经报道了肿瘤坏死因子-α（TNF-α）与重金属暴露之间的关系。然而，炎症反应中有毒金属和必需元素之间的相互作用仍不清楚。本研究旨在探讨血液中砷（As）、镉（Cd）、铅（Pb）、钴（Co）、铜（Cu）、硒（Se）和锌（Zn）与 TNF-α以及肾功能之间的关系。我们招募了 421 名工人，测量了这七种金属/类金属和 TNF-α在血液中的水平；通过 CKD-EPI 方程计算肾功能。我们应用加权分位数总和（WQS）回归和组 WQS 回归来评估金属/类金属混合物对 TNF-α和肾功能的影响。我们还通过广义加性模型（GAM）探讨了金属/类金属与 TNF-α之间的关系。在调整了协变量后，发现 Pb 水平与血清中 TNF-α之间的暴露-反应曲线关系呈显著非线性（p < 0.001）。在多金属模型中，Pb、As 和 Zn 与 TNF-α水平升高有关，其效应分别专门归因于混合物的 50%、31%和 15%。分组 WQS 表明必需金属组与 TNF-α和肾功能呈显著负相关。有毒金属组与 TNF-α、血清肌酐和白细胞计数呈显著正相关，但与 eGFR 无关。这些结果表明，Pb、As、Zn、Se 和混合物可能通过相互作用机制对 TNF-α产生影响。我们的研究结果提供了一些见解，即金属混合物的哪些主要成分在金属共同暴露期间会影响炎症和肾功能；然而，其机制仍需要进一步研究。
