Effects of sub-acute exposure to TiO₂, ZnO and Al₂O₃nanoparticles on oxidative stress and histological changes in mouse liver and brain

Abstract

Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. However the information regarding toxicity of these nanoparticles on humans and environment is still deficient. The present study investigated the toxic effects of three metal oxide nanoparticles, TiO2, ZnO and Al2O3 on mouse erythrocytes, brain and liver. Male mice were administered a single oral dose of 500 mg/kg of each nanoparticles for 21 consecutive days. The results suggest that exposure to these nano metallic particles produced a significant oxidative stress in erythrocyte, liver and brain as evident from enhanced levels of Reactive Oxygen Species (ROS) and altered antioxidant enzymes activities. A significant increase in dopamine and norepinephrine levels in brain cerebral cortex and increased brain oxidative stress suggest neurotoxic potential of these nanoparticles. Transmission electron microscopic (TEM) analysis indicated the presence of these nanoparticles inside the cytoplasm and nucleus. These changes were also supported by the inhibition of CuZnSOD and MnSOD, considered as important biomarkers of oxidative stress. The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide and titanium dioxide, respectively. The present results further suggest the involvement of oxidative stress as one of the main mechanisms involved in nanoparticles induced toxic manifestations.

Zinc oxide nanoparticles induce toxic responses in human neuroblastoma SHSY5Y cells in a size-dependent manner

“…15 Various studies have shown that ZnO NPs with various shapes, such as rods and spheres, probably cause neurotoxicity due to their ability to access the brain. [16][17][18] Moreover, the olfactory brain route has also been reported as a potential route for ZnO NPs transfer into the brain. 19 However, information regarding the neurotoxic effects of ZnO NPs is scarce.…”

Effects of aluminum, copper, and titanium nanoparticles onsome blood parameters in Wistar rats

“…Many studies showed that metals can induce oxidative stress by generating free radicals and ROS, and the liver and kidney have antioxidant defense systems to protect animals from oxidative stress caused by metals (Jorgensen, 2010). NPs were regarded as one of the main mechanisms involved in induced toxic manifestations in animals, as they can penetrate inside the cytoplasm and nucleus (Shrivastava et al, 2013). The present data demonstrated that total oxidant levels in the serum of rats increased considerably, though total antioxidant levels did not follow this trend, suggesting possible oxidative stress.…”

“…Syama et al (2013) showed that there was a concentration-dependent fall in cell viability, a decrease in antioxidant enzyme levels, and an increase in DNA adduct of the liver of mice following zinc NP exposures. Shrivastava et al (2013) studied the effects of TiO 2 , ZnO, and Al 2 O 3 NPs on oxidative stress in the erythrocytes, liver, and brain of male mice following oral administration of NPs for 21 days. They found that there was significant production of ROS and consecutively antioxidant enzyme activities altered, supporting the present results.…”

Potential Links between Cytoskeletal Disturbances and Electroneurophysiological Dysfunctions Induced in the Central Nervous System by Inorganic Nanoparticles

“…Some studies have reported that inorganic NPs could pass through the BBB through several pathways ( Fig. 1) and accumulate in different regions of the brain [10][11][12] through different mechanisms and processes. For example, insulin-targeted gold NPs had been reported to cross the BBB by receptor-mediated endocytosis [13], and reduced graphene oxide was found to impair BBB integrity by downregulating the TJ protein occludin and the adherens junction protein β-catenin in vivo [14].…”