New evidence on the nephrotoxicity of fine particulate matter: Potential toxic components from different emission sources

Associations exist between fine particulate matter (PM_2.5) exposure and impaired kidney function. However, the specific mechanisms and components causing renal damage remain unclear. PM_2.5 was collected from an industrial and a rural area. Mice were categorized according to exposure, and biochemical, western blotting, histological, and immunohistochemical analyses were performed to evaluate the impact of PM_2.5 constituents on their kidneys. To assess the impact of different PM_2.5 components on inflammatory responses, a study was conducted by exposing the murine macrophage cell line (RAW 264.7). The study used a chelating resin to remove the influence of heavy metals from the water extract and employed a Toll-like receptor 4 (TLR4) antagonist to eliminate the effects of endotoxin, thereby evaluating the cellular inflammatory responses induced by various PM_2.5 components. The major metallic elements at the industrial site were Fe, Mg, Zn, and Ca, whereas those at site Rural were Ca, K, and Mg. PM_2.5 water extracts from both sites induced inflammatory cytokine upregulation in the lungs and kidneys, and inflammatory cell infiltration, antioxidant activity downregulation, and elevated levels of kidney injury molecule 1 in the kidneys. Exposure to PM_2.5 water extract increased the mRNA levels of tumor necrosis factor-α, interleukin-6, and nitrite production in RAW264.7 macrophages. The inflammatory response and nitrite production induced by the industrial-site PM_2.5 water extract were significantly suppressed after treatment with a chelating resin, whereas those from the rural area were suppressed by the Toll-like receptor 4 (TLR4) antagonist. These results suggest that heavy metals are crucial factors in PM_2.5-induced cellular inflammatory responses in industrial areas, whereas endotoxin receptor--TLR4 mediated inflammatory pathways are the primary factor responsible for this response in rural areas. Furthermore, at equivalent dosages, the renal toxicity induced by the water-soluble components of rural-site PM_2.5 may exceed that from industrial areas.