The Hazards of Fine Particulate Matter on Mice Kidney: Effects from Different Emission Sources and Potential Toxic Components

Abstract

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. The impact of different PM_2.5 components on inflammatory responses was assessed by exposing the murine macrophage cell line (RAW 264.7); a chelating resin, which removed heavy metals from the water extract, allowed for evaluating the inflammatory effects caused by various PM_2.5 constituents. 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. Compared to industrial-site PM_2.5, rural-site PM_2.5 significantly upregulated inflammatory cytokine infiltration in the lungs, increased inflammatory cell levels in the kidneys, and significantly increased kidney Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells. Exposure to PM_2.5 water extract increased the mRNA levels of tumor necrosis factor-α and 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 that in the rural area were suppressed by the Toll-like receptor 4 (TLR4) antagonist. At equivalent dosages, renal toxicity induced by the rural-site PM_2.5 water-soluble components might exceed that from industrial areas. Metal components may be crucial factors in PM_2.5-induced cellular inflammatory responses in industrial areas, while TLR4-mediated inflammatory pathways were a major factor responsible for this response in the rural area.