Synergistic Toxicity Of Zinc Oxide Nanoparticles And Cadmium Chloride In Mice

The wide applications of zinc oxide nanoparticles (nano ZnO) and ubiquitous cadmium (Cd) pollution have increased the risk of humans’ co-exposure to nano ZnO and Cd. Because of high catalytic activity and large specific surface area, nano zinc oxide can interact with biological molecules and induce the increasing of reactive oxygen species, leading to the accumulation of reactive oxygen species in organism, resulting in oxidative stress. Cadmium is a highly toxic heavy metal for most organisms. The cadmium-induced oxidative stress, epigenetic changes and the inhibition of transport in body is the most toxicity of cadmium elements in organisms. Other pathology mechanisms of cadmium toxicity include competitive inhibition of zinc and magnesium, inhibition of the synthesis of Ferrous red element, mitochondria damages or apoptosis. Cadmium may combine with mercapto group and makes protein structure distortion. In addition, cadmium can reduce glutathione. Here, we investigate the synergistic effects of nano ZnO and cadmium chloride (CdCl2) on their biodistribution and synergistic toxicity in mice.Chapter1:We briefly review the toxicity of nano ZnO and CdCl2. Nano ZnO can cause different toxicity response to cell and organism. The size, surface characteristic and exposure route of nano ZnO is the key factors of toxicity. The toxicity mechanisms of nano ZnO include oxidative stress, coordination effects and metabolic disturbance of zinc. On the other hand, Cadmium widely exists in natural environment, industrial goods and waste residue. Cadmium may entry into the bodies through the food chain and induce toxicity. The synergistic toxicity of nano ZnO and cadmium is still not clear. It is necessary to identify the synergistic effect of co-exposure to nano ZnO and CdCl2.Chapter2:In order to investigate the synergistic toxicity of nano ZnO and CdCl2, the coefficients of organs, histopathological changes and serum biochemical parameters were determined after intraperitoneal injection of nano ZnO and/or CdCl2to mice daily for7days. The results showed that exposure to nano ZnO caused silghtly damage in mice, but exposure to CdCl2caused siginificant damage in mice. Co-exposure to nano ZnO and CdCl2significantly attenuated CdCl2-induced damage in the liver as indicated by the slight liver dysfunction and histopathological abnormalities.Chapter3:We studied the synergistic effects of co-treatment with nano ZnO and CdCl2on the oxidative stress in the liver and kidney. Exposure to nano ZnO did not cause obvious oxidative stress in the liver and kidney. By contrast, exposure to CdCl2caused significant oxidative stress in the two organs. Co-exposure to nano ZnO and CdCl2led to slightly decreases in the SOD and GSH-Px activities in the liver compared with the either nano ZnO or CdCl2group, indicating that co-exposure induces less oxidative stress in the liver than exposure to either nano ZnO or CdCl2alone. The results showed that co-exposure to nano ZnO and CdCl2significantly attenuated CdCl2-induced damage in the liver.Chapter4:To investigate the mechanism of the synergistic toxicity of co-exposure to nano ZnO and CdCl2on toxicity, we have investigated the biodistribution of Zn and Cd in mice. Co-exposure to nano ZnO and CdCl2resulted in the synergistic accumulation of Zn and DM in the liver. Zn-and Cd-induced metallotbionein synthesis contributed to the positive synergistic uptake of Zn and Cd in the liver. The increase in metallothionein synthesis and the reduction of Cd-induced perturbation of Zn2+homeostasis after co-exposure to nano ZnO and CdCl2should take two important roles in the protective effect of nano ZnO on CdGl2-induced oxidative damage in the liver.