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ToxSci Advance Access originally published online on July 27, 2009
Toxicological Sciences 2009 111(2):392-401; doi:10.1093/toxsci/kfp164
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Published by Oxford University Press 2009.

Differential Pulmonary Retention of Diesel Exhaust Particles in Wistar Kyoto and Spontaneously Hypertensive Rats

Rajiv K. Saxena*,{dagger}, M. Ian Gilmour{dagger}, Mette C. Schladweiler{dagger}, Michael McClure{ddagger}, Michael Hays{ddagger} and Urmila P. Kodavanti{dagger},1

* School Of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India {dagger} Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 {ddagger} National Risk Management Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

1 To whom correspondence should be addressed at Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, 109 TW Alexander Drive, Research Triangle Park, NC 27711. E-mail: kodavanti.urmila{at}epa.gov.

Received May 7, 2009; accepted July 16, 2009


   Abstract

Spontaneously hypertensive (SH) and normotensive Wistar Kyoto (WKY) rats have been used for understanding the mechanisms of variations in susceptibility to airborne pollutants. We examined the lung burden of diesel exhaust particles (DEP) following inhalation of diesel engine exhaust (DEE) in both strains. The kinetics of clearance was also examined after single intratracheal (IT) instillation of DEP. Lungs were analyzed for DEP elemental carbon (EC) after exposure to DEE (0, 500, or 2000 µg/m3 4 h/day, 5 days/week x 4 weeks). SH rats had 16% less DEP-EC at 500 and 32% less at 2000 µg/m3 in the lungs, despite having 50% higher than the average minute volume. No strain-related differences were noted in number of alveolar macrophages or their average DEP load as evident from examining cells in bronchoalveolar lavage fluid (BALF). The kinetics of DEP clearance from lungs of male WKY and SH rats was studied following a single instillation at 0.0 or 8.33 mg/kg of DEP standard reference material (SRM 2975) from the National Institute of Standards Technology. SH rats cleared 60% DEP over 112 days while minimal clearance occurred from the lungs of WKY. The pattern of DEP-induced inflammatory response assessed by BALF analysis was similar in both strains, although the overall protein leak was slightly greater in SH rats. A time-dependent accumulation of DEP occurred in tracheal lymph nodes of both strains (SH > WKY). Thus, SH rats may clear DEP more efficiently from their lungs than normotensive WKY rats, with a small contribution of more effective lymphatic drainage.

Key Words: diesel exhaust particles; lung clearance; Wistar Kyoto rats; spontaneously hypertensive rats; hypertension; lymph nodes; lymphatic drainage.


Disclaimer: The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency and approved for publication. Approval does not signify that the contents necessarily reflect the views and the policies of the agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.


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