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Cardiovascular Effects of Pulmonary Exposure to Titanium Dioxide Nanoparticles in ApoE Knockout Mice

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Existing studies on the inhalation toxicology of titanium dioxide (TiO2) have focused on possible carcinogenic capacity; however researches on the cardiovascular effect are limited, particularly in terms of susceptible animal models. The present study examined the inhalation toxicology of nano-TiO2 in ApoE knockout mice (ApoE−/− mice), an atherosclerosis susceptible animal model. The nano-TiO2 particles used were anatase type and the diameter ranged from 5 to 10 nm. ApoE−/− mice were randomly divided into five groups (high dose group, median dose group, low dose group, PBS vehicle control group and the nontreatment control group), each of which were given tracheal instillation of nano-TiO2 at the dose of 100 μg, 50 μg and 10 μg and PBS solution per week respectively, totally for six weeks, while the nontreatment control group received no tracheal instillation. We measured various indicators of inflammation, endothelial dysfunction and lipid metabolism in serum, and determined plaque formation on the aorta. After six weeks of treatment, there was significant difference between the high dose group and PBS control group in terms of C reactive protein (CRP), nitric oxide (NO), endothelial nitric oxide synthases (eNOS), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) in serum. The results also showed ratio of plaque area to luminal area and the ratio of the lipid-rich core area to plaque area in the median and high nano-TiO2 dose group significantly increased respectively in HE stained cross-sections. Our study showed that tracheal instillation of nano-TiO2 particles induced considerable systemic inflammation, endothelial dysfunction and lipid metabolism dysfunction, contributing to the progression of atherosclerosis.
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Document Type: Research Article

Publication date: 2013-05-01

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  • Journal for Nanoscience and Nanotechnology (JNN) is an international and multidisciplinary peer-reviewed journal with a wide-ranging coverage, consolidating research activities in all areas of nanoscience and nanotechnology into a single and unique reference source. JNN is the first cross-disciplinary journal to publish original full research articles, rapid communications of important new scientific and technological findings, timely state-of-the-art reviews with author's photo and short biography, and current research news encompassing the fundamental and applied research in all disciplines of science, engineering and medicine.
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