Hindawi Publishing Corporation Journal of Toxicology Volume 2010, Article ID 206057, 12 pages doi:10.1155/2010/206057 Research Article Diesel Engine Exhaust Initiates a Sequence of Pulmonary and Cardiovascular Effects in Rats Ingeborg M. Kooter, 1, 2 Miriam E. Gerlofs-Nijland, 2 A. John F. Boere, 2 Daan L. A. C. Leseman, 2 Paul H. B. Fokkens, 2 Henri M. H. Spronk, 3 Kim Frederix, 3 Hugo ten Cate, 3 Ad M. Knaapen, 4, 5 Hendrik J. Vreman, 6 and Flemming R. Cassee 2 1 Department of Environment, Health and Safety, TNO Built, Environment and Geosciences, Princetonlaan 6, 3584 CB Utrecht, The Netherlands 2 Centre for Environmental Health Research, National Institute for Public Health and the Environment, 3720 BA Bilthoven, The Netherlands 3 Department of Internal Medicine, Laboratory of Clinical Thrombosis and Haemostasis, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands 4 Department of Health Risk Analysis and Toxicology, Nutrition and Toxicology Research Institute (NUTRIM), Maastricht University, 6229 ER Maastricht, The Netherlands 5 Organon, Schering Plough, 5342 CC Oss, The Netherlands 6 Division of Neonatal & Developmental Medicine, Department of Pediatrics, Stanford University Medical Center, Stanford, CA 94305-5208, USA Correspondence should be addressed to Ingeborg M. Kooter, ingeborg.kooter@tno.nl Received 16 June 2010; Accepted 27 September 2010 Academic Editor: JeanClare Seagrave Copyright © 2010 Ingeborg M. Kooter et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This study was designed to determine the sequence of events leading to cardiopulmonary effects following acute inhalation of diesel engine exhaust in rats. Rats were exposed for 2 h to diesel engine exhaust (1.9 mg/m 3 ), and biological parameters related to antioxidant defense, inflammation, and procoagulation were examined after 4, 18, 24, 48, and 72h. This in vivo inhalation study showed a pulmonary anti-oxidant response (an increased activity of the anti-oxidant enzymes glutathione peroxidase and superoxide dismutase and an increase in heme oxygenase-1 protein, heme oxygenase activity, and uric acid) which precedes the inflammatory response (an increase in IL-6 and TNF-α). In addition, increased plasma thrombogenicity and immediate anti- oxidant defense gene expression in aorta tissue shortly after the exposure might suggest direct translocation of diesel engine exhaust components to the vasculature but mediation by other pathways cannot be ruled out. This study therefore shows that different stages in oxidative stress are not only affected by dose increments but are also time dependent. 1. Introduction Epidemiological studies have shown associations between daily changes in air pollution such as particulate matter (PM) and cardiopulmonary morbidity and mortality [1, 2]. Although the relative risk estimates are small, there is a serious public health concern because of the large number of people exposed and the existence of high risk groups, such as the elderly and people with cardiopulmonary diseases. PM can be considered a complex chemical mixture that may have various effects on pulmonary and cardiovascu- lar tissues depending on its physicochemical properties. There is, however, a need to obtain better insight into the plausibility of the PM-associated health effects for risk assessment purposes. This information can be obtained from studies focusing on the processes underlying the health effects of PM. Several mechanisms have been postulated and include injury of pulmonary epithelial tissue, inflammation, and oxidative stress response. In addition, extrapulmonary