Ultrafine Particulate Ferrous Iron and Anthracene Associations with Mitochondrial Dysfunction

Abstract

The ultrafine size fraction of ambient particles (ultrafine particles [UFP], diameter < 100 nm) has been identified as being particularly potent in their adverse health effects, yet, the detailed mechanisms for why UFP display such distinctive toxicity are not well understood. In the present study, mitochondria were exposed to ambient UFP while monitoring mitochondrial electron transport chain (ETC) activity as a model system for biochemical toxicity. UFP samples were collected in rural and urban environments, and chemically characterized for trace metals, ferrous (Fe(II)) and easily reducible ferric (Fe(III)) iron, polycyclic aromatic hydrocarbons (PAHs), and surface constituents with X-ray photoelectron spectroscopy (XPS). Fixed doses of UFP (8 μg mL⁻¹) inhibited mitochondrial ETC function compared to controls in 94% of the samples after the 20 min of exposure. Significant moderate to weak correlations exist between initial %ETC inhibition (0 – 10 min) and Fe(II) (R = 0.55, P = 0.03, N = 15), anthracene (R = 0.74, P < 0.01, N = 13), and %C–O surface bonds (R = 0.56, P = 0.03, N = 15), whereby anthracene and %C–O correlate with each other (R = 0.58, P = 0.03, N = 14). Multivariate linear regression showed that when combined, Fe(II) and anthracene best describe the initial %ETC inhibition (R = 0.91, P = 0.00, N = 14). No significant associations were identified with total Fe and other trace metals. Results from this study indicate that Fe(II) and anthracene-related, C–O containing, surface structures may contribute to the initial detrimental behavior of UFP, also supporting the idea that the Fe(II)/Fe(III) and certain efficient hydroquinone/quinone redox pairs play important roles due to their potential to produce reactive oxygen species (ROS).