Jiangxue Wang

Time-dependent translocation and potential impairment on central nervous system by intranasally instilled TiO2 nanoparticles

Nanoparticles can be administered via nasal, oral, intraocular, intratracheal (pulmonary toxicity), tail vein and other routes. Here, we focus on the time-dependent translocation and potential damage of TiO(2) nanoparticles on central nervous system (CNS) through intranasal instillation. Size and structural properties are important to assess biological effects of TiO(2) nanoparticles. In present study, female mice were intranasally instilled with two types of well-characterized TiO(2) nanoparticles (i.e. 80 nm, rutile and 155 nm, anatase; purity>99%) every other day. Pure water instilled mice were served as controls. The brain tissues were collected and evaluated for accumulation and distribution of TiO(2), histopathology, oxidative stress, and inflammatory markers at post-instillation time points of 2, 10, 20 and 30 days. The titanium contents in the sub-brain regions including olfactory bulb, cerebral cortex, hippocampus, and cerebellum were determined by inductively coupled plasma mass spectrometry (ICP-MS). Results indicated that the instilled TiO(2) directly entered the brain through olfactory bulb in the whole exposure period, especially deposited in the hippocampus region. After exposure for 30 days, the pathological changes were observed in the hippocampus and olfactory bulb using Nissl staining and transmission electron microscope. The oxidative damage expressed as lipid peroxidation increased significantly, in particular in the exposed group of anatase TiO(2) particles at 30 days postexposure. Exposure to anatase TiO(2) particles also produced higher inflammation responses, in association with the significantly increased tumor necrosis factor alpha (TNF-alpha) and interleukin (IL-1 beta) levels. We conclude that subtle differences in responses to anatase TiO(2) particles versus the rutile ones could be related to crystal structure. Thus, based on these results, rutile ultrafine-TiO(2) particles are expected to have a little lower risk potential for producing adverse effects on central nervous system. Although understanding the mechanisms requires further investigation, the present results suggest that we should pay attention to potential risk of occupational exposure for large-scaled production of TiO(2) nanoparticles.

Potential neurological lesion after nasal instillation of TiO2 nanoparticles in the anatase and rutile crystal phases

Nanoscale titanium dioxide (TiO(2)) is massively produced and widely used in living environment, which hence make the potential risk to human health. Central nervous system (CNS) is the potential susceptible target of inhaled nanoparticles, but the studies on this aspect are limited so far. We report the accumulation and toxicity results in vivo of two crystalline phases of TiO(2) nanoparticles (80nm, rutile and 155nm, anatase; purity >99%). The female mice were intranasally instilled with 500microg of TiO(2) nanoparticles suspension every other day for 30 days. Synchrotron radiation X-ray fluorescence analysis (SRXRF) and inductively coupled plasma mass spectrometry (ICP-MS) were used to determine the contents of titanium in murine brain. Then, the pathological examination of brain tissue, oxidative stress-mediated responses, and levels of neurochemicals in the brain of exposed mice were also analyzed. The obvious morphological changes of hippocampal neurons and increased GFAP-positive astrocytes in the CA4 region were observed, which were in good agreements with higher Ti contents in the hippocampus region. Oxidative stress occurred obviously in whole brain of exposed mice such as lipid peroxidation, protein oxidation and increased activities of catalase, as well as the excessive release of glutamic acid and nitric oxide. These findings indicate anatase TiO(2) nanoparticles exhibited higher concern on some tested biological effects. To summarize, results provided the preliminary evidence that nasal instilled TiO(2) nanoparticles could be translocated into the central nervous system and cause potential lesion of brain, and the hippocampus would be the main target within brain.

Elimination efficiency of different reagents for the memory effect of mercury using ICP-MS

The present study was carried out to solve the problems of long washout time and non-linear calibration curves encountered in mercury analysis using inductively coupled plasma mass spectrometry. Comparisons of the washing efficiency for different reagents to eliminate the mercury memory effect were made. Of all the selected washing reagents, mercapto reagents such as 2-mercaptoethanol and L-cysteine could efficiently clean the instrument. Taking the toxicity and odor of mercaptoalkanol into account, L-cysteine was preferred as the most suitable washing reagent and was added into the standard and sample solutions. A good linear calibration curve was obtained with the correlation coefficient of 0.9999. The detetion limit for addition of L-cysteine was 0.024 μg l−1. Addition of 0.18% L-cysteine into the sample solution also facilitates the washout of mercury even using deionized water. The recoveries of mercury in certified reference materials, i.e. human hair and dogfish muscle, were 97.2% and 98.3%, respectively, when using 0.18% L-cysteine in the sample solutions.

Simultaneous speciation of selenium and mercury in human urine samples from long-term mercury-exposed populations with supplementation of selenium-enriched yeast by HPLC-ICP-MS

The present study was carried out to establish a method for simultaneous speciation analysis of selenium and mercury. Batch-wise elution using two different mobile phases that are suitable for selenium and mercury speciation leads to successful determination of both selenium and mercury standards in 30 minutes with good efficiency and resolution. The detection limits are in the range of 0.05–0.3 μg L−1 for selenium species, except TMSe, which has a poorer detection limit (1.48 μg L−1), and 2.5 μg L−1 for inorganic mercury (Hg2+) and 2.0 μg L−1 for organic mercury (CH3Hg+). The method was applied to analysis of urine samples from people who were long-term mercury exposed and supplemented with selenium-enriched yeast for 90 days. Selenocystine (SeCys) was found to be a major selenium form, while inorganic mercury is the major mercury form. The recoveries of spiked species were between 93 and 117% in all cases. The increased mercury concentrations in urine after 90-day selenium supplementation suggest that selenium is beneficial to the excretion of mercury from urine. The proposed technique may help to increase our understanding of the in vivo interaction between selenium and mercury in human body.

BIOLOGICAL EFFECT OF INTRANASALLY INSTILLED TITANIUM DIOXIDE NANOPARTICLES ON FEMALE MICE

The toxicological effect of TiO2 nanoparticles with different crystal structure (80 nm for rutile and 155 nm for anatase) on female mice was investigated through intranasal instillation. After exposure for 30 days at the dose of 50 mg/kg body weight, no abnormal activity and mortality were observed with the normally increasing body weight of mice. The coefficients of tissues to body weight also show no obvious difference from the control except the increased coefficient of kidneys in mice exposed to 80 nm TiO2 nanoparticles. Titanium contents and histopathology examination indicate the no pathological response in the lung was induced by the increased TiO2 deposition, and the liver, heart, and spleen were not influenced. The severe pathology changes in kidneys suggest that TiO2 nanoparticles may be excreted out by kidneys via system circulation. However, the serum biochemical parameters were not changed compared with the control, which means no obvious functional impairment induced by the nasal exposure for 30 days. In addition, the higher titanium contents in the brain tissues imply that the translocation and deposition of nanoparticles through intranasal instilling pathway is different from the other routes such as intratracheal inhalation or intratracheal instillation. The influence of deposited nanoparticles on central nervous system needs further investigation and is underway.