Relationship between pulmonary exposure to multiple doses of single wall carbon nanotubes and atherosclerosis in ApoE-/- mouse model.
Li-ZJ; Chapman-R; Hulderman-T; Salmen-R; Shvedova-A; Luster-MI; Simeonova-PP
Toxicologist 2006 Mar; 90(1):318
Epidemiological studies are demonstrating a link between exposure to air pollutants and cardiopulmonary diseases. Recent studies showed that single installation of single wall carbon nanotubes (SWCNT) into the lung of C57BL/6 mice results in pulmonary granuloma formation and fibrosis. We demonstrated that this response is associated with dose-dependent oxidative effects including mitochondrial DNA damage and protein carbonyl formation in the aortic tissue. Consistently, SWCNT exposure induces similar oxidative modifications in the aortic tissue of ApoE-/- mice. The chronic vascular oxidative modifications might lead to accelerated atherosclerosis. To test this hypothesis, ApoE-/- mice (10 mice per treatment) were exposed by pharyngeal aspiration to SWCNT (20 ug/mouse) or vehicle via multiple exposures (once every other week for 8 weeks). The mice were on a chow diet for four weeks followed by four weeks on a cocoa butter diet (TD 88051; Harlan). At the end of the exposure period the lungs and the atherosclerotic lesions were assessed histopathologically. The experimental treatment resulted in nanotube accumulation in the lung and foci of granuloma formation accompanied with different degree of inflammatory and fibrotic responses. The percent of plaque area in the aortas, measured by en face method, was significantly increased in the SWCNT treated mice (p<0.01). Furthermore, a significant increase in atherosclerotic lesion size was demonstrated by histopatological morphometrical analysis of serial sections of the brachiocephalic arteries (p<0.001). The body weight, plasma high/low density cholesterol, and liver enzymes were similar between the controls and the treated mice. In conclusion, pulmonary exposure to multiple doses of SWCNT induces severe lung toxicity and accelerates the progression of atherosclerosis in ApoE-/- mice. The atherogenic effects might be a result of low-grade systemic inflammatory responses related to the lung toxicity and/or translocation of nanotubes into the systemic circulation.
Models; Laboratory-animals; Animals; Animal-studies; Epidemiology; Pulmonary-system-disorders; Respiratory-system-disorders; Lung-disorders; Lung-fibrosis; Fibrosis; DNA-damage; Nanotechnology
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California