Abstract

Particulate air pollution has been associated with increased risk of cardiopulmonary diseases. However, the underlying mechanisms are not fully understood. We have previously demonstrated that single dose exposure to diesel exhaust particle (DEP) causes lung inflammation and peripheral thrombotic events. Here, we exposed mice with repeated doses of DEP (15µg/animal) every 2nd day for 6 days (a total of 4 exposures), and measured several cardiopulmonary endpoints 48 h after the end of the treatments. Moreover, the potential protective effect of curcumin (the yellow pigment isolated from turmeric) on DEP-induced cardiopulmonary toxicity was assessed. DEP exposure increased macrophage and neutrophil numbers, tumor necrosis factor α (TNF α) in the bronchoalveolar lavage (BAL) fluid, and enhanced airway resistance to methacoline measured invasively using Flexivent. DEP also significantly increased plasma C-reactive protein (CRP) and TNF α concentrations, systolic blood pressure (SBP) as well as the pial arteriolar thrombosis. It also significantly enhanced the plasma D-dimer and plasminogen activator inhibitor-1 (PAI-1). Pretreatment with curcumin by oral gavage (45 mg/kg) 1h before exposure to DEP significantly prevented the influx of inflammatory cells and the increase of TNF α in BAL, and the increased airway resistance caused by DEP. Likewise, curcumin prevented the increase of SBP, CRP, TNF α, D-dimer and PAI-1. The thrombosis was partially but significantly mitigated. In conclusion, repeated exposure to DEP induced lung and systemic inflammation characterized by TNFα release, increased SBP, and accelerated coagulation. Our findings indicate that curcumin is a potent anti-inflammatory agent that prevents the release of TNFα and protects against the pulmonary and cardiovascular effects of DEP.

Highlights

  • A number of epidemiological studies reported strong and consistent associations between exposure particulate air pollution and increase of respiratory and cardiovascular morbidity and mortality [1,2]

  • Cell composition and number in bronchoalveolar lavage (BAL) fluid Depending on the i.t. treatment performed, the cells found in BAL were primarily macrophages and PMN

  • Curcumin pretreatment significantly prevented the influx of inflammatory cells and the increase of TNFa concentrations in BAL

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Summary

Introduction

A number of epidemiological studies reported strong and consistent associations between exposure particulate air pollution and increase of respiratory and cardiovascular morbidity and mortality [1,2]. In this context, epidemiological time-series studies have identified an association between daily changes in concentration of ambient air pollution and daily number of deaths and hospitalizations, from cardiovascular disease and following relatively short time lags after exposure peaks [1,2]. The ambient level of black carbon particles, used as a tracer for traffic pollution, has been consistently associated with a variety of adverse health outcomes [1,2]. The exact mechanistic pathways are still not fully understood

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