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Pulmonary responses to diesel fuel catalyst cerium oxide nanoparticles.
Ma-JY; Zhao-H; Barger-M; Rao-M; Meighan-T; Castranova-V; Ma-J
Toxicologist 2009 Mar; 108(1):49
Cerium oxide has been used as a fuel-borne catalyst to lower the mass of diesel exhaust particles (DEP), but is emitted as nanoparticles in the diesel exhaust. While the health effects of DEP have been investigated for decades, the potential pulmonary toxicity of cerium oxide nanoparticles has not been characterized. The objectives of this study were to investigate the effects of cerium oxide on the pulmonary immune/inflammatory responses. Rats (Sprague Dawley) were exposed to cerium oxide (0.5 to 20 mg/kg) by intratracheal instillation. Alveolar macrophages (AM) were isolated via bronchoalveolar lavage (BAL) the next day. Cerium oxide exposure was found to induce significant neutrophil infiltration and elevate lactate dehydrogenase activity and albumin content in the BAL fluid, suggesting that these particles induced inflammation, cytotoxicity and epithelial damage. The results also show a direct interaction of cerium oxide with AM, resulting in elevated AM phagocytic activity as monitored using confocal microscopy, increased reactive oxygen species production in response to zymosan challenge as indicated by enhanced chemiluminscence generation, and increased production of the pro-inflammatory cytokines IL-12 and TNF-alpha. However, cerium oxide significantly reduced nitric oxide production by AM in response to ex vivo LPS challenge, demonstrating that these particles may modify AM host defense capability. Analysis of mRNA levels of several genes using real time RT-PCR indicate that cerium oxide significantly increased suppressor of cytokine signaling and osteopontin (OPN) in BAL cells, while OPN was also increased in the lung tissue. When OPN was analyzed at 28 days post exposure, there was a further increase of mRNA in lung tissue. These results show that cerium oxide-mediated lung toxicity includes pulmonary inflammation and lung injury, and a persistent induction of OPN in lung tissue, which has been associated with lung fibrosis.
Breathing; Breathing-zone; Diesel-emissions; Diesel-exhausts; Exposure-assessment; Exposure-levels; Exposure-methods; Genetic-factors; Genotoxic-effects; Immune-reaction; Immune-system; Immunotoxins; Lung-disorders; Lung-irritants; Lung-fibrosis; Mathematical-models; Models; Particle-aerodynamics; Particulate-dust; Pulmonary-disorders; Pulmonary-system; Pulmonary-system-disorders; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Statistical-analysis; Nanotechnology
Issue of Publication
The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland