Effects of cerium oxide nanoparticles on diesel exhaust particles-induced pulmonary responses.
Ma-JY; Mercer-RR; Barger-M; Ma-JK; Castranova-V
Toxicologist 2012 Mar; 126(Suppl 1):68
Diesel exhaust particles (DEP) are the major constituent of ambient particulate that are known to induce lung inflammation and injury. When using cerium compounds as diesel engine catalyst to lower DEP emission, cerium oxide nanoparticles (CeO2) were detected in the exhaust. Our previous studies have shown that CeO2 not only induces pulmonary inflammation, but also lung fibrosis. In this study, we investigated the effects of CeO2, DEP and their combination on pulmonary responses pertaining to lung inflammation and fibrosis. Male Sprague Dawley rats were exposed to DEP with or without CeO2 (20% w/w) by a single intratracheal instillation and sacrificed at 1, 10 and 28 days after exposure. Bronchial alveolar lavage (BAL) was performed; cellular and acellular fractions of BAL fluid were obtained; and particle-induced lung inflammation, cellular toxicity, and alveolar air/blood barrier damage were determined through monitoring PMN infiltration, LDH activity, and albumin content in the first BAL fluid. The DEP-induced responses were acute and transient, peaked at 1-day after exposure, but significantly declined at 10- and 28-day post exposure. However, CeO2+DEP induced inflammatory responses were found persistent throughout the 28-day exposure period. DEP-exposed alveolar macrophages induced oxidant and nitric oxide generation and proinflammatory cytokine, TNF-á and IL-12, production. The presence of CeO2 markedly reduced DEP-induced cellular responses. At 28 days post exposure, CeO2- and CeO2+DEP-exposed lungs showed significantly induced phospholipidosis and hydroxyproline content in lung tissues. Morphological analysis showed that both DEP and CeO2+DEP demonstrated granulomatos lesions. However, there were more cells and collagen in CeO2+DEP- than DEP-exposed lungs. These results suggest that exposure of rats to CeO2+DEP induced sustained inflammatory lung injury and enhanced fibrotic development compared to exposure to DEP alone. These findings suggest potential health effects of CeO2 when used as diesel engine catalyst are of concern.
Nanotechnology; Laboratory-animals; Laboratory-techniques; Laboratory-testing; Exposure-assessment; Exposure-methods; Exposure-levels; Heart; Lung; Pulmonary-system; Immune-reaction; Dose-response; Vasoactive-agents; Particulates; Diesel-exhausts
Transportation, Warehousing and Utilities
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California