Microglial activation, recruitment and phagocytosis as linked phenomena in ferric oxide nanoparticle exposure.

Microglia as the resident macrophage-like cells in the central nervous system (CNS) play a pivotal role in the innate immune responses of CNS. Understanding the reactions of microglia cells to nanoparticle exposure is important in the exploration of neurobiology of nanoparticles. Here we provide a systemic mapping of microglia and the corresponding pathological changes in olfactory-transport related brain areas of mice with Fe(2)O(3)-nanoparticle intranasal treatment. We showed that intranasal exposure of Fe(2)O(3) nanoparticle could lead to pathological alteration in olfactory bulb, hippocampus and striatum, and caused microglial proliferation, activation and recruitment in these areas, especially in olfactory bulb. Further experiments with BV2 microglial cells showed the exposure to Fe(2)O(3) nanoparticles could induce cells proliferation, phagocytosis and generation of ROS and NO, but did not cause significant release of inflammatory factors, including IL-1ß, IL-6 and TNF-α. Our results indicate that microglial activation may act as an alarm and defense system in the processes of the exogenous nanoparticles invading and storage in brain.

Endothelial dysfunction and inflammation induced by iron oxide nanoparticle exposure: Risk factors for early atherosclerosis.

More recently, the correlation between exposure to nanoparticles and cardiovascular diseases is of particular concern in nanotoxicology related fields. Nanoparticle-triggered endothelial dysfunction is hypothesized to be a dominant mechanism in the development of the diseases. To test this hypothesis, iron oxide nanoparticles (Fe2O3 and Fe3O4), as two widely used nanomaterials and the main metallic components in particulate matter, were selected to assess their potential risks on human endothelial system. The direct effects of iron oxide nanoparticles on human aortic endothelial cells (HAECs) and the possible effects mediated by monocyte (U937 cells) phagocytosis and activation were investigated. In the study, HAECs and U937 cells were exposed to 2, 20, 100 µg/mL of 22-nm-Fe2O3 and 43-nm-Fe3O4 particles. Our results indicate that cytoplasmic vacuolation, mitochondrial swelling and cell death were induced in HAEC. A significant increase in nitric oxide (NO) production was induced which coincided with the elevation of nitric oxide synthase (NOS) activity in HAECs. Adhesion of monocytes to the HAECs was significantly enhanced as a consequence of the up-regulation of intracellular cell adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8) expression, all of which are considered as early steps of atheroscelerosis. Phagocytosis and dissolution of nanoparticles by monocytes were found to simultaneously provoke oxidative stress and mediate severe endothelial toxicity. We conclude that intravascular iron oxide nanoparticles may induce endothelial system inflammation and dysfunction by three ways: (1) nanoparticles may escape from phagocytosis that interact directly with the endothelial monolayer; (2) nanoparticles are phagocytized by monocytes and then dissolved, thus impact the endothelial cells as free iron ions; or (3) nanoparticles are phagocytized by monocytes to provoke oxidative stress responses.

In vitro cytotoxicity of transparent yellow iron oxide nanoparticles on human glioma cells.

With rapid development of nanotechnology, concerns about the possible adverse health effects on human beings by using nanomaterials have been raised. Transparent yellow iron oxide (alpha-FeOOH) nanoparticles have been widely used in paints, plastic, rubber, building materials, papermaking, food products and pharmaceutical industry, thus the potential health implications by the exposure should be considered. The purpose of this study is to assess the cytotoxicity of transparent yellow iron oxide nanoparticles on U251 human glioma cells. The alpha-FeOOH nanoparticles are in clubbed shapes with 9 nm in diameter and 43 nm long. The specific surface area is 115.3 m2/g. After physicochemical characterization of the nanoparticles, U251 cells were exposed to a-FeOOH at the doses of 0, 3.75, 15, 60 and 120 microg/mL. The results showed that the alpha-FeOOH nanoparticles reduced the cell viability and induced necrosis and apoptosis in U251 cells. In addition, nanoparticle exposure significantly increased the levels of superoxide anion and nitric oxide in a dose-dependent fashion in the cells. Our results suggest that exposure to alpha-FeOOH nanoparticles induce significant free radical formation and cytotoxic effects. The large surface area that induced high surface reactivity may play an important role in the cytotoxic effect of alpha-FeOOH nanoparticles.

Using ion-pair reversed-phase HPLC ICP-MS to simultaneously determine Cr(III) and Cr(VI) in urine of chromate workers.

Urinary chromium speciation analysis can provide available information of the individual exposure levels of Cr(VI) compounds. An analytical method based on ion-pair reversed-phase HPLC combined with ICP-MS to simultaneously determine Cr(III) and Cr(VI) in human urine has been developed for assessing the occupational exposure to chromate. The separation conditions of the method, including the pH value, the concentrations of ion-pair reagent and methanol in the mobile phase were studied. Specially, a high-speed polyetheretherketone (PEEK) column and a typical sample introduction method were employed to avoid the exogenous chromium contamination during the analysis. The separation of Cr(III) and Cr(VI) could be finished within 4min with the detection limits as low as 0.03microgL(-1) at 100microL injections for both of them, providing a convenient method for routine analysis of chromium species. The chromium species in urine of chromate workers were monitored using the developed method. The statistical analysis showed a significant relationship (n=32, p<0.01) between the urinary Cr(VI) and the individual airborne exposure levels, indicating that the urinary Cr(VI) could be used as a convenient and suitable monitor for high level Cr(VI) occupational exposure.