Urinary oxidative stress biomarkers in nephrotoxicity induced by PM2.5 in a rat model.

Abstract

Objective: The present study evaluated urinary oxidative stress (OxS) biomarkers to explain the extrapulmonary effect of renal function decline due to subchronic inhalation exposure to particles smaller than 2.5 μm, as well as the correlation of the biomarkers with the particles' endotoxin content.

Materials and methods: Adult male Sprague-Dawley rats were exposed to subchronic inhalation of particles smaller than 2.5 μm (8 weeks, 4 days/week, 5 h/day). The control group was exposed to filtered air. MiniVol and HiVol samplers were used to estimate the concentration and collected particles, respectively. Biomarkers were assessed in weekly urine samples harvested by the metabolic cage. The OxS biomarkers assessed were methylglyoxal, non-esterified fatty acids, malondialdehyde, advanced oxidative protein products, arginase, myeloperoxidase, glutathione S-transferase, and gamma-glutamyl transferase, all of which were evaluated by colorimetric assays. Creatinine was evaluated by the Jaffe reaction, and cystatin-C (Cys-C) and neutrophil gelatinase-associated lipocalin-2 were quantified using Luminex technology. Endotoxin content was analyzed with the Limulus Amebocyte Lysate Pyrochrome Chromogenic Test Kit.

Results and discussion: Subchronic exposure to PM_2.5 increased OxS biomarkers in urine. Endotoxin content showed a positive correlation with the urinary OxS biomarkers evaluated. Additionally, urinary OxS biomarkers correlated with creatinine and the early kidney damage biomarkers Cys-C and neutrophil gelatinase-associated lipocalin-2, where the strongest and positive correlations were observed with the latter two biomarkers.

Conclusions: Inhalation of environmental airborne particles smaller than 2.5 μm increased urinary OxS biomarkers, correlated with endotoxin content and early kidney damage biomarkers. This finding corroborates the extrapulmonary nephrotoxic effect of inhaled particles.