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Contrasting Actions of Diesel Exhaust Particles on the Pulmonary and Cardiovascular Systems and the Effects of Thymoquinone

Nemmar A, Al-Salam S, Zia S, Marzouqi F, Al-Dhaheri A, Subramaniyan D, Dhanasekaran S, Yasin J, Ali BH, Kazzam EE. Contrasting actions of diesel exhaust particles on the pulmonary and cardiovascular systems and the effects of thymoquinone. 1. Br J Pharmacol. 2011 Dec;164(7):1871-82. doi: 10.1111/j.1476-5381.2011.01442.x.

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 ?g?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 ?g?mL(-1 border=0> 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.