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Pulmonary carbon nanotube exposure and oxidative status in vascular system.
Li Z; Salmen R; Hulderman T; Kisin E; Shvedova A; Luster M; Simeonova P
Free Radic Biol Med 2004 Nov; 37(Suppl 1):S142-S143
Cardiovascular diseases, which in majority of cases stem from atherosclerosis, continue to be the principal cause of death in the United States. In addition to personal factors like hyperlipidemia and obesity, some environmental factors including cigarette smoking and air pollution, have been associated with cardivascular diseases. Engineered nanosized particles, such as carbon nanotubes (CNT), are new materials of emerging technological importance in different industries. The unique physical characteristics of these particles raise concerns that they may have not only pulmonary toxicity but also be associated with extra-pulmonary toxicity including heart and vessels. In the present study, we hypothesized that CNT pulmonary exposures can induce oxidative changes in the vasculature related to atherogenesis. C57BL/6 mice were exposed to CNT in doses (0.5; 1; 2 mg/kg) by single intra-pharyngeal installation and the mice were sacrificed at different time points (1; 7; 28; 56 days) after the exposure (the experimental settings have been related to pulmonary toxicity). Genomic DNA was isolated from the aortas of these mice and the oxidative effects were measured by extra long quantitative PCR of mitochondrial (mt)DNA. We found that CNT exposures are associated with dose-dependent aortic mtDNA damage at day 7, 28 and 56 after exposure. MtDNA damage might be a direct result from CNT which penetrate to the circulation or an indirect result of the lung inflammation. The direct oxidative potential of CNT was evaluated in vitro by measuring the mtDNA damage in human aortic endothelial cells (HAEC) as well as the oxidation of low density lipoproteins (LDL) in the presence of HAEC. CNT dose dependently induced oxidative modifications in this in vitro system. In conclusion, CNT induces direct or indirect oxidative effects which might be predisposing factors for atherogenesis.
Cardiovascular-system-disorders; Cardiovascular-system-disease; Cardiovascular-disease; Mortality-data; Environmental-factors; Smoking; Air-contamination; Pollution; Pulmonary-system-disorders; Respiratory-system-disorders; Exposure-levels; Lung-disorders; In-vitro-studies; Nanotechnology
Free Radical Biology and Medicine
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