We hypothesize that inhaled ambient ultrafine (UF) particles can induce oxidative stress-related injury of target cells in the cardiovascular system, thus providing a plausible mechanism for adverse effects observed in sensitive populations. We measured pulmonary and cardiovascular endpoints related to inflammation and oxidative stress in a diabetic rat model after exposure to concentrated UF/fine particle- containing aerosols. The Harvard ultrafine concentrated ambient particle system (HUCAPS) was used to generate the aerosols (particle number concentration ~0.05-1.3 x 106/cm3; count median diameter ~75 nm) for acute exposures (4 hrs; 3 x 6 hrs). Obese, insulin-resistant homozygous male JCR:LA-cp rats (cp/cp; 13-15 months) as well as non-diabetic, lean heterozygous males (+/?; 5-13 months) were exposed to the HUCAP aerosols; controls were exposed to particle-filtered air. We collected blood, bronchoalveolar lavage fluid, and several tissues (lungs, heart, carotid arteries, aorta, liver, pancreas, spleen, kidneys, brain) after exposure. JCR cp/cp rats had slightly higher total lung lavage cell numbers, more blood leukocytes and leukocyte aggregates, and less glial fibrillary acidic protein in brain. These parameters were not consistently affected by HUCAP exposure. Although lavage neutrophils remained unchanged, there was a trend towards elevated protein, lactate dehydrogenase, and â-glucuronidase in HUCAP-exposed rats that was independent of genotype or exposure duration. After 3 days of exposure, the amplification of aortic mitochondrial DNA (12 kb) was significantly decreased in HUCAP-exposed cp/cp rats as compared to +/? rats and air-exposed controls. These results show that small oxidant stress-related changes occur after acute exposure to real-world particles in an animal model relevant to the study of UF particle effects in humans.
Laboratory-animals; Animal-studies; Biodynamics; Pulmonary-disorders; Pulmonary-function-tests; Pulmonary-system-disorders; Alveolar-cells; Lung-cells; Lung-irritants; Lung-function; Air-contamination; Air-monitoring; Air-quality; Particulate-dust; Particulates; Particle-aerodynamics; Models; Cardiopulmonary-system-disorders; Cardiovascular-system-disorders; Nanotechnology
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina