Department of Chemistry, University of Torino, Torino 10125, Italy.
IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf 40225, Germany.
Chem Res Toxicol. 2021 Mar 15;34(3):767-779. doi: 10.1021/acs.chemrestox.0c00399. Epub 2021 Mar 2.
Transition metals play a key role in the pathogenic potential of urban particulate matter (PM). However, air quality regulations include exposure limits only for metals having a known toxic potential like Pb, As, Cd, and Ni, neglecting other transition metals like Fe and Cu. Fe and Cu are mainly found in the water-soluble fraction of PM. However, a fraction of the ions may persist strongly bound to the particles, thus potentially acting as surface reactive sites. The contribution of surface ions to the oxidative potential (OP) of PM is likely different from that of free ions since the redox activity of metals is modulated by their local chemical environment. The aim of this study was to investigate how Fe and Cu bound to carbonaceous particles affect the OP and associated toxicity of PM toward epithelial cells and macrophages. Carbonaceous nanoparticles (CNPs) having well-defined size were loaded with controlled amounts of Cu and Fe. The effect of Cu and Fe on the OP of CNPs was evaluated by electronic paramagnetic resonance (EPR) spectroscopy associated with the spin-trapping technique and correlated with the ability to induce cytotoxicity (LDH, WST-1), oxidative stress (Nrf2 translocation), and DNA damage (comet assay) on lung macrophages (NR8383) and/or epithelial cells (RLE-6TN). The release of pro-inflammatory cytokines (TNF-α, MCP-1, and CXCL2) by macrophages and epithelial cells was also investigated. The results indicate a major contribution of surface Cu to the surface reactivity of CNPs, while Fe has a minor role. At the same time, Cu increases the cytotoxicity of CNPs and their ability to induce oxidative stress and DNA damage. In contrast, surface Fe increases the release of pro-inflammatory cytokines by macrophages. Overall, these results confirm the role of Cu and Fe in PM toxicity and suggest that the total metals content in PM might be a better indicator of pathogenicity than water-soluble metals.
过渡金属在城市颗粒物（PM）的致病潜力中起着关键作用。然而，空气质量法规仅包括对具有已知毒性潜力的金属（如 Pb、As、Cd 和 Ni）的暴露限制，而忽略了其他过渡金属，如 Fe 和 Cu。Fe 和 Cu 主要存在于 PM 的水溶性部分。然而，一部分离子可能与颗粒强烈结合而持久存在，从而可能作为表面反应性位点。表面离子对 PM 的氧化潜力（OP）的贡献可能与游离离子不同，因为金属的氧化还原活性受其局部化学环境的调节。本研究旨在探讨与碳质颗粒结合的 Fe 和 Cu 如何影响 PM 的 OP 及其对上皮细胞和巨噬细胞的相关毒性。具有明确定义尺寸的碳质纳米颗粒（CNP）负载有控制量的 Cu 和 Fe。通过电子顺磁共振（EPR）光谱结合自旋捕获技术评估 Cu 和 Fe 对 CNP 的 OP 的影响，并将其与诱导细胞毒性（LDH、WST-1）、氧化应激（Nrf2 易位）和 DNA 损伤（彗星试验）的能力相关联在肺巨噬细胞（NR8383）和/或上皮细胞（RLE-6TN）上。还研究了巨噬细胞和上皮细胞中促炎细胞因子（TNF-α、MCP-1 和 CXCL2）的释放。结果表明，表面 Cu 对 CNP 的表面反应性有很大贡献，而 Fe 的作用较小。同时，Cu 增加了 CNP 的细胞毒性及其诱导氧化应激和 DNA 损伤的能力。相比之下，表面 Fe 增加了巨噬细胞释放促炎细胞因子的能力。总的来说，这些结果证实了 Cu 和 Fe 在 PM 毒性中的作用，并表明 PM 中的总金属含量可能比水溶性金属更能指示其致病性。
