The Synergistic Subacute Toxicity Of ZnO Nanoparticles And Dimethoate In Mice

The extensive applications of nanomaterials and organophosphorus chemicals have increased the risk of humans’ co-exposure to nanomaterials and organophosphorus chemicals. They can enter into environmentals during their production, store, transportation and consumption, cause environmental pollution, and are uptaken by organism through the food chain. Many studies indicated that both of nanomaterials and organophosphorus chemicals can induce oxidative stress via production generation of free radicals and alteration of antioxidant statues. However, their synergistic toxicity is still unclear. Here, we investigate the synergistic effects of ZnO nanoparticles (ZnO-NPs) and dimethoate (DM) on their biodistribution and subacute toxicity in mice.Chapter 1:We briefly review the toxicity of ZnO-NPs and DM. ZnO-NPs can cause different toxicity response to cell, aquatic ecosystems and organism. The size, surface characteristic, solution and exposure route of ZnO-NPs is the key factors of toxicity. The toxicity mechanisms of ZnO-NPs include oxidative stress, coordination effects and non-homeostasis. Currently, the abundant residue of DM and its analog in environment are uptaken by organisms through food chain. The inhibition of cholinesterase and disturbance of antioxidant enzymes system has been reported as the two main mechanisms of DM toxicity. It is necessary to identify the synergistic effect of co-exposure to ZnO-NPs and DM.Chapter 2:In order to identify the synergistic toxicity, the coefficients of organs, histopathological changes and serum biochemical parameters were determined after intraperitoneal injection of ZnO-NPs and/or DM to mice daily for 14 days. In vivo results showed that ZnO-NPs and DM have a positive synergistic toxicity in mice. Exposure to DM caused siginificant damage mainly in the liver. Although ZnO-NPs at a dose of 20 mg/kg BW were low toxic to mice, co-exposure to ZnO-NPs and DM significantly enhanced DM-induced damage in the liver as indicated by the severe liver dysfunction and histopathological abnormalities such as inflammatory cell infiltration, spotty necrosis and mesothelial hyperplasia.Chapter 3:We studied the synergistic effects of co-treatment with ZnO-NPs and DM on the oxidative stress in the liver and kidney. Exposure to ZnO-NPs does not cause obvious oxidative stress in the liver and kidney. By contrast, exposure to DM causes significant oxidative stress in the two organs. Co-exposure to ZnO-NPs and DM led to significant decreases in the SOD and GSH-Px activities in the liver and significantly higher MDA concentrations in the liver compared with the either ZnO-NPs or DM group, indicating that co-exposure induces more severe oxidative stress in the liver than exposure to either ZnO-NPs or DM alone. In addition, the significant inhibition of cholinesterase activity in liver of mice after co-exposure to ZnO-NPs and DM, indicates that ZnO-NPs significantly enhance the toxicity of DM.Chapter 4:In order to investigate the mechanism of a synergistic toxicity of co-exposure on toxicity, we have investigated the biodistribution of Zn and DM in vivo, and the binging of BSA and DM to ZnO-NPs in vitro. Co-exposure to ZnO-NPs and DM resulted in the synergistic accumulation of Zn and DM in the liver, which is a key factor for the positive synergistic toxicity. In vitro binding assays indicated that serum albumin and DM mutually enhanced the binding of each other to ZnO-NPs via the interaction of serum albumin and DM. The uptake of serum albumin-and DM-bound ZnO-NPs by the macrophages significantly increased DM accumulation in mice, resulting in enhance their toxicity. Therefore, the synergistic binding of serum protein and DM to ZnO-NPs is the main mechanism of the positive synergistic effects of co-exposure on their toxicity. In addition, the results demonstrate that serum albumins play an important role in the positive synergistic toxicity of ZnO-NPs and DM.