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Inhaled ultrafine (nano) particles can translocate into the bloodstream and interact with circulatory cells causing systemic and cardiovascular events. To gain more insight into this potential mechanism, we studied the interaction of diesel exhaust particles (DEP) with human, rat and mouse erythrocytes in vitro. Incubation of erythrocytes with DEP (1, 10 or 100 μg/ml) for 30 min caused the highest hemolytic effect (up to 38%) in rats, compared to small but significant hemolysis in mice (up to 2.5%) and humans (up to 0.7%). Transmission electron microscopy of erythrocytes revealed the presence of variable degrees of ultrafine (nano)-sized aggregates of DEP either internalized and/or adsorbed onto the erythrocytes in the three species. A significant amount of DEP was found in rat and mouse (but not human) erythrocytes. Lipid erythrocyte susceptibility to in vitro peroxidation measured by malondialdehyde showed a significant and dose-dependent increase in erythrocytes of rats, but not humans or mice. Unlike in human erythrocytes, total antioxidant status (TAS) and superoxide dismutase (SOD) activity in rats were significantly and dose- dependently decreased. In mouse erythrocytes, DEP caused a decreased in SOD (at 10 μg/ml) and TAS (at 100 μg/ml) activities. In conclusion, DEP caused species–dependent erythrocyte hemolysis and oxidative stress, and were either taken up and/or adsorbed onto the red blood cells. Rat (and to a lesser degree mouse) erythrocytes were susceptible to DEP. Human erythrocytes showed the highest resistance to the observed effects. These species difference should be noted when using rats and mice blood as models for humans. [ABSTRACT FROM AUTHOR]

Abstract: Several epidemiological studies have shown that acute exposure to particulate air pollution is associated with increases in cardiovascular morbidity and mortality, and that these effects are especially exacerbated among individuals with pre-existing compromised cardiovascular function such as hypertension. This study was undertaken to determine the cardiovascular effect of diesel exhaust on TO mice made hypertensive by implanting osmotic minipump infusing angiotensin II or vehicle (control). On day 13, the animals were intratracheally instilled with either DEP (15μg/mouse) or saline. 24h later, pulmonary exposure to DEP had significantly decreased the systolic blood pressure (SBP) in hypertensive (HT) mice (P <0.01), but not in normotensive (NT) mice. The number of leukocytes and red blood cells, and the plasma interleukin 6 concentration in plasma, however, were not affected in any of the animals. The PaO2 was decreased, and PaCO2 increased in DEP-treated HT mice compared to NT mice treated with DEP (P <0.05). The number of circulating platelets was significantly increased in DEP-treated HT versus saline-treated HT and DEP-treated NT mice. Moreover, in NT mice, DEP exposure induced a prothrombotic effect in pial arterioles compared with saline-treated NT mice (P <0.05). Interestingly, in DEP-treated HT mice, the prothrombotic events were significantly aggravated compared with saline-treated HT and DEP-treated NT mice. The direct addition of DEP (0.1–1μg/ml) to untreated mouse blood significantly induced in vitro platelet aggregation in a dose-dependent fashion, and these effects were more pronounced in blood of HT mice. In vitro exposure to DEP (0.25–1μg/ml) led to activated intravascular coagulation, an effect that was confirmed by a shortening of both the activated partial thromboplastin time (aPTT) and the prothrombin time (PT). The effect of DEP on aPTT was potentiated in the plasma of HT mice. It can be concluded that the thrombotic events caused by DEP are exacerbated by hypertension in mice. Our findings, therefore, provide a possible plausible explanation for the cardiovascular morbidity and mortality accompanying urban air pollution. [Copyright &y& Elsevier]

Inhaled particles are associated with pulmonary and extrapulmonary effects. Also, acute renal failure (ARF) is associated with increased mortality, related to pulmonary complications. Here, we tested the possible potentiating effect of diesel exhaust particles (DEP) in an animal model of ARF induced by a single ip injection of cisplatin (CP, 6 mg/kg) in rats. Six days later, the rats were intratracheally instilled with either DEP (0.5 or 1 mg/kg) or saline (control) and renal, systemic, and pulmonary variables were studied 24 h thereafter. CP increased the serum concentrations of urea and creatinine and reduced glutathione (GSH) concentration and superoxide dismutase activity in renal cortex. CP caused renal tubular necrosis; increased urine volume, protein concentrations, and N-acetyl-β-D-glucosaminidase (NAG) activity; and decreased urine osmolality. The combination of DEP and CP aggravated the CP-induced effects on serum urea and creatinine, urine NAG activity, and renal GSH. The arterial O2 saturation and PO2 were significantly decreased in CP + DEP versus CP + saline and CP + DEP versus DEP. The number of platelets was reduced in DEP compared to saline-treated rats and CP + DEP versus DEP alone or CP + saline. Increases in macrophage and neutrophils numbers in bronchoalveolar lavage were found in DEP versus saline group and CP + DEP versus CP. Histopathological changes in lungs of DEP-treated rats were aggravated by the combination of CP + DEP. These included marked interstitial cell infiltration and congestion. We conclude that the presence of DEP in the lung aggravated the renal, pulmonary, and systemic effects of CP-induced ARF. [ABSTRACT FROM PUBLISHER]

Abstract: Exposure to particulate matter is a risk factor for respiratory and cardiovascular diseases. However, the mechanisms underlying these effects are not well understood. Here, we compared the impact of diesel exhaust particles (DEP) on airway resistance, inflammation and oxidative stress in normal mice, or mice made hypertensive by implanting osmotic minipump infusing angiotensin II. On day 13 after the onset of infusion, angiotensin II induced significant increase in heart rate (P <0.05) and systolic blood pressure (P <0.0001). On the same day, mice were intratracheally instilled with either DEP (15μg/mouse) or saline. Twenty-four hour later, the measurement of airway reactivity to methacholine (0–10mg/ml) in vivo by a forced oscillation technique showed a significant and dose dependent increase in airway resistance in normotensive mice exposed to DEP compared to those exposed to saline. In hypertensive mice, there was no difference in airway resistance in DEP versus saline exposed mice. However, following exposure to DEP, airway resistance significantly increased in normotensive versus hypertensive mice. Bronchoalveolar lavage (BAL) fluid analysis showed a significant increase in macrophage numbers in normotensive mice exposed to DEP compared to those exposed to saline, and to hypertensive mice exposed to DEP. Neutrophil numbers were significantly increased in both normotensive and hypertensive mice exposed to DEP compared with their respective control groups. Superoxide dismutase activity was significantly decreased following DEP exposure in both normotensive and hypertensive mice compared to their respective controls. However, total proteins, a marker for increase of epithelial permeability, and malondialdehyde, a reflection of lipid peroxidation, were only increased in normotensive mice exposed to DEP. Therefore, our data suggest that DEP do not aggravate airway resistance and inflammation in angiotensin II-induced hypertensive mice. On the contrary, at the dose of DEP and time point investigated, airway resistance, inflammation and oxidative stress are increased in normotensive compared to hypertensive mice. [Copyright &y& Elsevier]

Abstract: Nanosized fraction of particulate air pollution has been reported to translocate from the airways into the bloodstream and act on different organs. However, the direct effect of these translocated particles is not well understood. In this study, we determined the time-course (6h, 18h, 48h and 168h) effects of the systemic administration of 0.02mg/kg diesel exhaust particles (DEP) on systolic blood pressure (SBP), systemic inflammation, oxidative status, and morphological alterations in lungs, heart, liver and kidneys in Wistar rats. SBP was significantly decreased at 6h (P <0.05) but no significant effects have been observed at later time points. The leukocyte numbers were increased at 6h (P <0.05) and 18h (P <0.05). However, the platelet numbers were significantly decreased (P <0.05) 6h following the systemic administration of DEP. The IL-6 concentrations in plasma was increased at 6h (P <0.05) and 18h (P <0.05). Similarly, superoxide dismutase activity was significantly increased at 6 (P =0.01) and 18h (P <0.05) following DEP exposure. The direct addition of DEP (0.1–1μg/ml) to untreated rat blood significantly induced in vitro platelet aggregation in a dose-dependent fashion. The activation of intravascular coagulation was confirmed by a dose-dependent shortening of activated partial thromboplastin time and the prothrombin time following in vitro exposure to DEP (0.25–1μg/ml). Histological analysis revealed the presence of DEP in the lungs, heart, liver and kidneys. However, the morphological changes were only observed in the lungs, where the presence of infiltration of inflammatory cells was observed as early as 6h, increased at 18h, and decreased in intensity at 48h and at 168h. We conclude that the direct systemic administration of DEP caused acute effect on SBP (6h) and systemic inflammation and oxidative stress mainly at 6h and 18h. Despite the presence of DEP in lungs, heart, liver and kidneys, the histopathological changes were only seen in the lung which suggests that, at the dose and time-points investigated, DEP cause inflammation and have a predilection for pulmonary tissue. [Copyright &y& Elsevier]