Search

Background and Purpose: Acute exposure to particulate air pollution has been linked to acute cardiopulmonary events, but the underlying mechanisms are uncertain. EXPERIMENTAL APPROACH We investigated the acute (at 4 and 18 h) effects of diesel exhaust particles (DEP) on cardiopulmonary parameters in mice and the protective effect of thymoquinone, a constituent of Nigella sativa. Mice were given, intratracheally, either saline (control) or DEP (30 µg·per mouse). KEY RESULTS At 18 h (but not 4 h) after giving DEP, there was lung inflammation and loss of lung function. At both 4 and 18 h, DEP caused systemic inflammation characterized by leucocytosis, increased IL-6 concentrations and reduced systolic blood pressure (SBP). Superoxide dismutase (SOD) activity was decreased only at 18 h. DEP reduced platelet numbers and aggravated in vivo thrombosis in pial arterioles. In vitro, addition of DEP (0.1-1 µg·mL(-1)) to untreated blood-induced platelet aggregation. Pretreatment of mice with thymoquinone prevented DEP-induced decrease of SBP and leucocytosis, increased IL-6 concentration and decreased plasma SOD activity. Thymoquinone also prevented the decrease in platelet numbers and the prothrombotic events but not platelet aggregation in vitro.Conclusions and Implications: At 4 h after DEP exposure, the cardiovascular changes did not appear to result from pulmonary inflammation but possibly from the entry of DEP and/or their associated components into blood. However, at 18 h, DEP induced significant changes in pulmonary and cardiovascular functions along with lung inflammation. Pretreatment with thymoquinone prevented DEP-induced cardiovascular changes. [ABSTRACT FROM AUTHOR]

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]

Abstract: Nanomaterials are extensively used in medicines, industry and daily life, but little is known about their possible health effects. Titanium dioxide (TiO2) nonmaterial-based photocatalysis is useful in the complete mineralization of organic pollutants in waste water and air. While the Fe-doping of TiO2 enhances their photocatalytic activity, their potential pathophysiologic effects are unknown. Here, rutile Fe-doped (9%) pure titanium dioxide (TiO2) nanorods were prepared and characterized. Subsequently, we assessed the acute (24h) pulmonary and extrapulmonary effects of intratracheal (i.t.) instillation of these nanorods (1 and 5mg/kg) in Wistar rats. In the bronchoalveolar lavage, the treatment induced a significant and dose-dependent increase of neutrophils, an increase of interleukin-6 (IL-6, at 5mg/kg), and caused a dose-dependent-decrease of superoxide dismutase (SOD) activity. The lung sections of rats exposed to rutile Fe–TiO2 nanorods showed infiltration of inflammatory cells in dose-dependent manner. Similarly, the heart rate, systolic blood pressure, plasma IL-6, and leukocyte and platelet numbers were increased at 5mg/kg. The plasma SOD and reduced glutathaione activities were dose-dependently decreased after exposure to the nanorods. Histopathologically, the liver showed mild inflammatory cells infiltration of few portal tracts, but the kidneys and heart were unaffected. In plasma, the levels of lactate dehydrogenase and hepatic enzymes, i.e., alanine aminotranferease and aspartate aminotransferase were increased significantly. The in vitro exposure of human lung cancer cells NCI-H460-Luc2 and human hepatoma cells HepG2 to FeTiO2 (6.25–100μg/ml) dose-dependently reduced cellular viability. Also, the In vitro direct addition of these nanorods (0.1–1μg/ml) to untreated rat blood, significantly and dose-dependently induced platelet aggregation. In conclusion, exposure to rutile Fe–TiO2 promotes pulmonary and systemic inflammation and oxidative stress. It affects the liver, enhances thrombotic potential, heart rate and systolic blood pressure. Moreover, the rutile Fe–TiO2 elicited direct toxicity on NCI-H460-Luc2 and HepG2 cells. [Copyright &y& Elsevier]