Neurotoxicity of aluminum oxide nanoparticles and their mechanistic role in dopaminergic neuron injury involving p53-related pathways.

The central nervous system is a potential target for Al2O3 nanoparticles (Nano-Al2O3). Here, we investigated the effects of intranasal instillation of Nano-Al2O3 on the distribution and damage in crucial functional sub-brain regions of rats. In vivo results show that Nano-Al2O3 was translocated into the brain via the olfactory nerve pathway. Nano-Al2O3 accumulated in the hippocampus, olfactory bulb, cerebral cortex, and striatum, causing ultrastructural changes, oxidative damage, inflammatory responses, and histopathological damage in sub-brain regions. As indicated by in vitro studies, cell viability decreased with the addition of Nano-Al2O3, which increased the levels of lactate dehydrogenase and oxidative stress. Nano-Al2O3 also impaired mitochondrial function, disturbed the cell cycle and induced apoptosis. In addition, Nano-Al2O3 decreased the expression of cyclin D1, bcl-2, Mdm2, and phospho-Rb and increased the expression of p53, p21, Bax, and Rb. Therefore, oxidative stress, mitochondrial dysfunction, and p53-related pathways might be important in the process of dopaminergic neurotoxicity induced by Nano-Al2O3. The current study establishes a striatum damage model and identifies molecular biomarkers of dopaminergic neuron damage induced by Nano-Al2O3. In brief, our study demonstrates that Nano-Al2O3 exposure can be a risk factor for neurodegenerative diseases and may negatively impact the hippocampus, striatum, and dopaminergic neurons.

Antagonistic effect of vitamin E on nAl2O3-induced exacerbation of Th2 and Th17-mediated allergic asthma via oxidative stress.

Some basic research has shown that nanomaterials can aggravate allergic asthma. However, its potential mechanism is insufficient. Based on the research that alumina nanopowder (nAl2O3) has been reported to cause lung tissue damage, the purpose of this study was to explore the relationship between nAl2O3 and allergic asthma as well as its molecular mechanism. In this study, Balb/c mice were sensitized with ovalbumin (OVA) to construct the allergic asthma model while intratracheally administered 0.5, 5 or 50 mg kg-1·day-1 nAl2O3 for 3 weeks. It was observed that exposure to nAl2O3 exacerbated airway hyperresponsiveness (AHR), airway remodeling, and inflammation cell infiltration, leading to lung function damage in mice. Results revealed that nAl2O3 could increase ROS levels and decrease GSH levels in lung tissue, promote the increases of the T-IgE, TGF-ß, IL-1ß and IL-6 levels, stimulate the overexpression of transcription factors GATA-3 and RORγt, decrease the levels of IFN-γ and IL-10 and increase the levels of IL-4 and IL-17A, resulting in the imbalance of Th1/Th2 and Treg/Th17 immune responses. In addition, antioxidant Vitamin E (Vit E) could alleviate asthma-like symptoms through blocking oxidative stress. The study displayed that exposure of nAl2O3 deteriorated allergic asthma through promoting the imbalances of Th1/Th2 and Treg/Th17.

Early Postnatal Exposure to Airborne Fine Particulate Matter Induces Autism-like Phenotypes in Male Rats.

Epidemiological studies have revealed that ambient fine particulate matter (PM2.5) exposure is closely associated with autism spectrum disorder (ASD). However, there is a relative paucity of laboratory data to support this epidemic finding. In order to assess the relationship between PM2.5 exposure and ASD, neonatal male Sprague-Dawley rats were chosen and exposed to PM2.5 (2 or 20 mg/kg body weight, once a day) by intranasal instillation from postnatal day 8 to 22. It was found that when exposed to PM2.5 in the early neonatal period for two weeks, both groups of the exposure rats manifested typical behavioral features of autism, including communication deficits, poor social interaction, and novelty avoidance. And, we further found, among five ASD candidate genes we chose, both the mRNA level and protein expression of SH3 and multiple ankyrin repeat domains 3 (Shank3) decreased significantly in the rat hippocampus after high dose of PM2.5 exposure. Moreover, results showed that PM2.5-exposure significantly increased the levels of proinflammatory cytokines, interleukin 1ß, interleukin 6, and tumor necrosis factor alpha in the hippocampus and prefrontal cortex. The expression of glial fibrillary acidic protein and ionized calcium-binding adapter molecule, markers of astrocytes and microglial cell activation, respectively, also increased in the exposed animals. Our work provides new data on the link between postnatal exposure to ambient PM2.5 and the onset of ASD-like symptoms in human beings, and the increased inflammatory response and abnormalities in Shank3 expression in the brain may contribute to the mechanisms of PM2.5 exposure-induced ASD.

Thyroid follicular lesions induced by thiazole-Zn feed treatment for one year in Sprague-Dawley rats.

Thiazole-Zn is a newly created Chinese systemic fungicide that is a thiadiazole compound. The toxicity of thiazole-Zn was examined in Sprague-Dawley rats fed diets containing 0, 4, 20 and 100mg/kg thiazole-Zn for one year. Lower body weight gains were noted in both males and females of the 100mg/kg diet group. Moreover, we show that the toxicity of thiazole-Zn was low, as evidenced by the absence of toxicologically significant changes in the general condition and appearance, hematology and clinical chemistry parameters, organ weights and necropsy findings of the rats. Thyroid follicular cell hyperplasia was the only finding of potential significance. The incidence of thyroid follicular cell hyperplasia significantly increased in high-dose males (4/10) and females (3/10) at the 26-week interim examination; one follicular adenoma in the thyroid was observed in high-dose males. At 52 weeks, the incidence of thyroid follicular cell hyperplasia was significantly higher in high-dose males (4/10) and females (4/10) than in the controls. Two thyroid follicular adenomas were observed in high-dose males. Other treatment-related effects and tumors at other sites were not observed. This study suggests that thiazole-Zn is a thyroid disrupter and likely a rat thyroid carcinogen.

Intraperitoneal injection of magnetic Fe3O4-nanoparticle induces hepatic and renal tissue injury via oxidative stress in mice.

Because of its unique magnetic properties, the iron oxide (Fe3O4) nanoparticle has been widely exploited and its application in various fields has promised immense benefits. However, doubts exist over the use of Fe3O4-nanoparticles in human beings. Thus, the aim of the current study was to find out the potential safety range of medical use. Twenty-five Kunming mice were exposed to Fe3O4-nanoparticles via intraperitoneal injection daily for 1 week at doses of 0, 5, 10, 20, and 40 mg/kg. Hepatic and renal tissues were sliced for physiological observation. Injuries were observed in the high-dose groups (20 and 40 mg/kg) compared with the control group (0 mg/kg). Biomarkers of reactive oxygen species, glutathione, malondialdehyde, DNA-protein crosslinks, and 8-hydroxy-2'-deoxyguanosine in the hepatic and renal tissues were detected. Injury to tissues and oxidative damage to cells at the molecular level was found. The safest dose recommended from the results of this study is 5 mg/kg, as we believe this to be an upper limit balancing the benefits and risks for sub-long-term exposure.

Biological evaluation of layered double hydroxides as efficient drug vehicles.

Recently there has been a rapid expansion of the development of bioinorganic hybrid systems for safe drug delivery. Layered double hydroxides (LDH), a variety of available inorganic matrix, possess great promise for this purpose. In this study, an oxidative stress biomarker system, including measurement of reactive oxygen species, glutathione content, endogenous nitric oxide, carbonyl content in proteins, DNA strand breaks and DNA-protein crosslinks, was designed to evaluate the biocompatibility of different concentrations of nano-Zn/Al-LDH with a Hela cell line. The drug delivery activity of the LDH-folic-acid complex was also assessed. The resulting data clearly demonstrated that nano-LDH could be applied as a relatively safe drug vehicle with good delivery activity, but with the caveat that the effects of high dosages observed here should not be ignored when attempting to maximize therapeutic activity by increasing LDH concentration.

[Primary study on the hepatotoxicity and nephrotoxicity of rats induced by three kinds of nanomaterials].

OBJECTIVE: To investigate the effects of hepatotoxicity and nephrotoxicity on rats induced by Nano-SiO2 Nano-Fe3O4 and SWCNTs. METHODS: 42 Wistar rats were randomly divided into the control group, low and high dose groups of three kinds of nanoparticles. The rats were killed when rats were exposed by oral gavage for 4 weeks. The ratios of liver and kidney to body weight, the pathological changes of liver and kidney, serum certain biochemically indexes were detected. RESULTS: The ratios of liver and kidney to body weight in experimental groups were not significantly difference in comparison to the control. The ALT and AST level in serum of rats in part experiment groups were more higher than those of the control group. The results of pathological analysis indicated that there were small amounts inflammatory cell infiltration and hepatic cell adipose degeneration in the liver of rats in high-dose group, the change of kidney were not found. CONCLUSION: Three kinds of nanoparticles could induce hepatotoxicity of the rats in the condition of this experiment.