Effects Of Combined Exposure To Nano Titanium Dioxide And Azoxystrobin On Heart Development Of Zebrafish Larvae

As a broad-spectrum and high-efficiency strobilurin fungicide,azoxystrobin（AZ）has been used for disease control of crops and frequently detected in aquatic environment.Nano titanium dioxide（n-TiO₂）is widely used,and the usage of it is increasing year by year.N-TiO₂will enter the water environment in the process of manufacturing,transportation and use.Mounting evidence indicated n-TiO₂has an adsorption effect on pollutants,which can change the bioaccumulation and toxicity of pollutants.Therefore,evaluating the toxic effect caused by n-TiO₂and AZ co-exposure should be attached great pmortance to.In this study,zebrafish embryos were exposed to AZ and n-TiO₂to explore the joint toxic effects of AZ and n-TiO₂on zebrafish heart development and its mechanism by analyzing AZ accumulation level,cardiac morphological and functional changes,ATPase activity,the expression level of calcium signaling pathway and oxidative phosphorylation-related genes.The key research results are as follows:1.N-TiO₂could adsorb AZ.The presence of n-TiO₂significantly reduced the bioaccumulation of AZ in zebrafish larvae in the high concentration AZ（1000μg/L）exposure.2.Acute exposure to AZ can lead to cardiac morphology and dysfunction by inducing pericardial edema,venous thrombosis,cardiac stretching,and heart rate disturbances.Cardiac histopathology analysis showed that AZ caused the loss of atrioventricular valves and the enlargement of cardiac myocytes.Meanwhile,AZ exposure also altered the expression of genes related to heart development.However,the preserence of n-TiO₂could alleviate AZ-induced cardiac toxicity.3.AZ exposure could induce the abnormality of calcium channel and the disorder of mitochondrial function,which is shown as concentration-dependent inhibition of total-At Pase and Ca²⁺-ATPase activities,while the activity of Na⁺K⁺-ATPase were promoted at low concentrations and inhibited at high concentrations.The expression of calcium channel and oxidative phosphorylation related genes was disordered.And n-TiO₂could alleviate the abnormality of calcium channel and mitochondrial dysfunction induced by AZ.In conclusion,AZ exposure can cause cardiotoxicity in zebrafish embryo.The dysfunction of calcium channel and oxidative phosphorylation may be the potential mechanism of cardiotoxicity,while AZ co-exposure with n-TiO₂can attenuate AZ accumulation in zebrafish larvae,thereby attenuatng AZ-induced cardiotoxicity.