Mechanistic Insights into the Role of Iron, Copper, and Carbonaceous Component on the Oxidative Potential of Ultrafine Particulate Matter

Abstract

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.

A perspective on iron (Fe) in the atmosphere: air quality, climate, and the ocean

“…Chemical toxicity studies that assess bioaccessibility of metals in PM use assays to quantify the fraction of soluble metal to accurately estimate the oxidative potential following inhalation-ingestion. 6,75 Most of the anions and organic acids in PM (described in detail below) are strong chelating agents for transition metals, and hence, identifying and quantifying their concentrations affect the bioavailability of metals and redox potential of PM. 76 Tacu et al 6 focused their toxicity studies on oxidative potential of Fe and Cu in the soluble fraction and surface of carbonaceous ultrane particles.…”

“…6,75 Most of the anions and organic acids in PM (described in detail below) are strong chelating agents for transition metals, and hence, identifying and quantifying their concentrations affect the bioavailability of metals and redox potential of PM. 76 Tacu et al 6 focused their toxicity studies on oxidative potential of Fe and Cu in the soluble fraction and surface of carbonaceous ultrane particles. They found that surface Fe(II) induces inammation and DNA damage, whereas Cu(I) is more reactive in oxidative stress and cytotoxicity.…”

“…[3][4][5] There is a growing concern in the public health community about the contribution of ultra-ne particles to human health. 6 Because of their small size, these particles can cross the mucous membrane and circumvent the blood-brain barrier into the central nervous system causing disruption and potential death of nerve cells. 7 Coordination of research from molecular to global scales is desirable because molecular-level understanding of mechanisms that affect the physicochemical processes of atmospheric aerosol particles help in parametrizing Fe mobilization, aerosol direct and indirect effect on the global climate.…”

Carbon nanoparticles adversely affect CFTR expression and toxicologically relevant pathways

“…In urban areas, particulate air pollution predominantly consists of ultrafine combustion-derived carbon particles 6 . Depending on the emitting source, these may be associated with contaminating toxicants like transition metals and organic compounds, including polycyclic aromatic hydrocarbons, that have been shown to contribute to their toxic effects [7][8][9] . Carbon nanoparticles (CNP) are considered a good model for the carbonaceous core of environmental ultrafine particles.…”

Significant association of urinary copper levels with bronchiectasis in non-smokers living in the vicinity of petrochemical complex: a population-based study

“…In vivo (C57BL/6 mice), copper oxide nanoparticles exposure induced expressions of the brosis marker α-SMA in the lung tissues linked to collagen accumulation and, indicating that copper oxide nanoparticles inhalation could induce pulmonary brosis(Lai et al 2018). In addition, in vitro study (rat alveolar type II epithelial cell line RLE-6TN), iron and copper that are mainly found in the water-soluble fraction of PM could induce oxidative stress and DNA damage(Tacu et al 2021). While biomarkers of the copperinduced pulmonary outcomes mainly focused on concentrations of sputum(Forte et al 2021), very few studies assessed the trace element concentrations in the urine, which may provide a valuable complementary approach to assess to risk patients.In addition to increasing age and exposure to tobacco smoke, exposure to other environmental and occupational hazards such as vapor, gases, dust, fumes, and tra c-related air pollution can increase the risk of interstitial lung abnormalities (ILA)(Hata et al.…”