Dados do Trabalho

Título

AIR POLLUTION AGGRAVATES ISCHEMIA/REPERFUSION-INDUCED AKI IN MICE

Introdução

In São Paulo, vehicle emissions are the main source of fine particulate matter (PM2.5). Epidemiological studies have linked PM2.5 exposure to an increased risk of CKD. The mechanisms mediating the adverse health effects of PM2.5 include epigenetic changes, oxidative stress and inflammation. The role of PM2.5 in AKI has yet to be described. We hypothesized that PM2.5 exposure would aggravate renal ischemia/reperfusion (I/R) injury in mice.

Material e Método

In temperature/humidity controlled chambers within an ambient particle concentrator, animals were exposed to a concentrated PM 2.5 stream (PM 2.5) or to high-efficiency particulate air-filtered clean air (CA). Mass concentrations of PM were measured with an airborne particulate monitor, and the target dose was 600 µg m −3 /day (equivalent of the daily exposure in SP). After 12 weeks, some PM 2.5 and CA mice underwent bilateral 30-min clamping of the kidney hila and subsequent reperfusion. All studies were performed 48 h after I/R. Groups: CA, PM 2.5 , CA+I/R and PM 2.5 +I/R. Data are mean±SEM.

Resultados

Creatinine clearance and urinary osmolality was lower in PM2.5+I/R compared to CA group (0.28±0.26 vs. 0.67±0.20 mL/min; p<0,05 and 1106±184 vs 2045±244 mOsm/kg; p<0,05 – respectively). Tubular Injury Score was higher in PM2.5+I/R compared to other groups (3.6±0.64 vs 0.00, 0.00 and 1.0±0.56, p<0,05). Renal Klotho protein expression was lower in PM2.5+I/R compared to other groups (1.1±0.24 vs. 4.7±0.8, 4.8±0.4 and 2.2±0.15, p<0,05). Renal tissue stain for F480, Ki67, ly6g, Caspase 3 and α-actin was higher in PM2.5+I/R compared to other groups (1.35±0.16 vs 0.71±0.15, 0.44±0.04, 0.83±0.11, p<0,05; 30.6±5.44 vs 1.55±0.41, 1.32±0.38 and 15.4±7.7, p<0,05 ; 61.84±11.29 vs 0.67±0.10, 1.10±0.20 and 12.19±6.55, p<0,05; 15.8 ± 5 vs 0.2 ± 0.09, 0.4 ± 0.14 and 2.8 ± 1.8, p<0,05; 7.4±0.7 vs 2.7±0.6, 1.1±0.1, 0.6±0.1; P<0.0001- respectively). Renal MnSOD and TLR4 proteins expression was higher in PM2.5+I/R than in CA+I/R, CA and PM2.5 (146±12 vs. 99±3.6, 102±3.9 and 96±2.8; p<0.05; 146±2.0, 128±2.1 vs. 97.5±2.1 and 98.0±0.9%; P<0.05—respectively). NGAL, RNAm expression and immunoassay levels were higher in PM2.5+I/R than other groups (115.2 ± 50 vs 2.4 ± 0.7, 4.2 ± 1.2 and 22.0 ± 9.0, p<0.05; 2.218,3±550,1 vs 4.044±546,7; P<0.03—respectively).

Discussão e Conclusões

PM2.5 aggravates I/R-induced AKI by decreasing renal Klotho protein, leading to increased renal Ngal, ki67, MnSOD, Caspase-3 expression and inflammatory cell infiltration. (FAPESP, NWO)

Palavras Chave

Aki, inflammation, air pollution, PM2.5