Protective Effect of Curcumin on Pulmonary and Cardiovascular Effects Induced by Repeated Exposure to Diesel Exhaust Particles in Mice

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.

The possible protective role of quercetin on induced cardiac Oxidative DNA Damage by repeated exposure to diesel exhaust nanoparticles in rats (a histological and immunohistochemical study)

“…They were suspended in sterile normal saline (NaCl 0.9%) containing tween 80 (0.01%)to decrease aggregation, Control group received only normal saline with 0.01% tween 80 [8].The collected particles were less than 2.5μm in size. Transmission Electron Microscope (HR-TEM) (JEOL 3010) was used for morphological analysis and seen the presence of nano-size particles.…”

“…Either the DENPs suspensions or normal saline only was intratracheallyinstilled using a sterile syringe [8]. The administration was done on days 1, 3, 4 and 7.…”

“…Studies on humans reported that exposure to DEP in a controlled manner resulted in elevated thrombus formation and endothelial dysfunction. Previous studies on lung cells and macrophages exposed to diesel exhaust nanoparticles (DENPs) indifferent concentrations demonstrated dose-dependent cytotoxicity, oxidative stress, inflammation, and DNA damage in cell lines [8]. Increased oxidative stress is detected in most types of HF, that resulting from ischaemic and non-ischaemic cardiomyopathy, pressure and volume overload, tachycardiomyopathy [9].…”

Amorphous silica nanoparticles impair vascular homeostasis and induce systemic inflammation

“…PAI-1 is the most potent endogenous inhibitor of fibrinolysis and is involved in the pathogenesis of several cardiovascular diseases. 34,35 An increase of PAI-1 has been observed following exposure to either DEP 36 or carbon nanotubes. 37 In conjunction with the fibrinolytic factor PAI-1, in the present study we measured the coagulation factor fibrinogen and found a significant increase following exposure to 50 nm SiNPs.…”

The acute pulmonary and thrombotic effects of cerium oxide nanoparticles after intratracheal instillation in mice

“…PAI-1 is a potent endogenous inhibitor of fibrinolysis and has been reported to increase following exposure to DEPs, silica NPs, and carbon nanotubes. [46][47][48] It has been shown that a 4-week inhalation exposure to DECe in rats induced an increase of tissue factor, but not in PAI-1 concentration. 19 The discrepancy between the latter study showing the absence of an increase of PAI-1 …”