Neurotoxicity Of Metal Oxide Nanoparticles

The term nanoparticle defines any particle less than 100 nm in at least one critical dimension. Due to their greater surface area, nanoparticles display properties not shown by their macroscopic counterparts, which have led to the rapid development of a new field, nanomedicine. However, nanomaterials could also be highly reactive and pose potential risks to humans due to their unique physiochemical properties. After entering the body by different routs, nanoparticles may translocate and reach other organs by different routes and mechanisms. The reticuloendothelial systems in liver and spleen are the major cleanup sites of nanoparticles via uptake by mononuclear phagocytes. However, nanoparticles unrecognized by reticuloendothelial system may have long circulation half-life and relocate to other target organs and induce inflammation via oxidative stress.Aluminium oxide, iron oxide and titanium oxide are widely used in industry and other fields, but safety information about these metal oxide nanoparticles is not sufficient until now. So, we observed the toxic effects of these metal oxide nanoparticles to N9 cell line and especially the toxicity of nano aluminium oxide to the brain and liver of rats in the experiments. This is a basic work to facilitate the risk assessment of neurotoxicity and liver toxicity induced by nano aluminium oxide.PartⅠ: Toxicity of metal oxide nanoparticles to N9 cell line Objective: To determine the toxice effects of metal oxide nanoparticles to N9 cell line. Method: The particle size and morphology of metal oxide nanoparticles in water were analyzed by electron microscope. The viability and apoptosis of N9 cell line were detected by MTT and Hoechst 33258, PI staining. Results: the diameters of metal oxide nanoparticles are less than 100nm with regular round shape. The cell viability of N9 is affect by the concentration of nanoparticles but not non-nanoparticles. The apoptosis of N9 cell line is induce by nanoparticles on a time- and dose-dependent manner. Conclusion: metal oxide nanoparticles have toxic effects to N9 cell line.Part II Tissue distribution of nano-scaled aluminium oxideObjective: To determine the tissue distribution of NAOs in rats. Method: 60 SD rats were randomly divided into 4 groups: control group, nNAOs group, NAOs group (1mg/kg), and NAOs group (50mg/kg). Each group was treated by intraperitoneal injection once two days. Rat tissues (liver, lung, kidney, spleen, hippocampus, and cerebral cortex) were taken out at five different time-points (2, 4, 8, 16, 30 day). Atomic absorption spectrometer (AAS) was used to detect the aluminum concentration in rat tissues samples. Results: NAOs were mainly distributed in spleen, liver, lung and kidney decreasingly, and its excretion was very quick in lung and liver. NAOs can't be seen significantly higher than control group in cerebral cortex and hippocampus. Conclusion: NAOs were maily distributed in spleen and liver, which have more reticulo-endothelial cells and phagocyte cells.Part III: Neurotoxicity of nano-scaled aluminium oxide to rats Objective: To study the toxic effect of nano-scaled aluminium oxide to rat brain tissues. Method: SD male rats were randomly divided into 4 groups: control group, nNAOs group, NAOs 1mg/kg group, and NAOs 50mg/kg group. Each group was treated by intraperitoneal injection once two days. Sixty days later, the content of malondialdehyde (MDA) and the activity of total-superoxide dismutase (T-SOD), catalase (CAT) and glutathione preoxidase (GSH-PX) in cerebral cortex, hippocampus were determined by optical meter. Expression of ED-1, EMAP II, GFAP and nestin was analyzed by immunohistochemistry. Results: In NAOs group, MDA levels in hippocampus, cerebral cortex were significantly higher than that of control group. The activity of GSH-PX in liver, T-SOD and GSH-PX in hippocampus and cerebral cortex were significantly higher. Massive expression of ED-1, GFAP was observed in the brain tissues. Conclusion: NAOs can induce enhanced lipid peroxidation and inflammation reaction in brain of rats, and this may play an important role in the toxicological mechanism of NAOs.Part IV: The toxic effects of nano-scaled aluminium oxide to rat liverObjective: To study the liver toxicity nano-scaled aluminium oxide to rats. Method: SD male rats were randomly divided into 4 groups: control group, nNAOs group, NAOs 1mg/kg and NAOs 50mg/kg. Each group was treated by intraperitoneal injection once two days. Real-time PCR was used to detect the apoptosis-related gene bax/bcl-2. Expression of ED-1, GFAP andβ-APP were detected by immunohistochemistry. The content of malondialdehyde (MDA) and the activity of total-superoxide dismutase (T-SOD), catalase (CAT) and glutathione preoxidase (GSH-PX) in cerebral cortex, hippocampus were determined by optical meter. Results: In NAOs group, the mRNA levels of bax and ratio of bax/bcl-2, were significant increased compared with control group. Conclusion: NAOs can increase the expression of apoptosis-related genes and induce inflammation as well as lipid peroxidation reaction in rat livers.