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

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.