Toxic effects of oxine-copper on development and behavior in the embryo-larval stages of zebrafish

Oxine-copper (OxCu) is generally used as an agricultural pesticide and induces harmful effects on ecosystems. In this study, zebrafish was used to assess the aquatic toxicity of OxCu. To detect the effects on development, embryos of 6 h post-fertilization (hpf) were exposed to 10 mu g/L, 20 mu g/L, 40 mu g/L OxCu for 18 h; meanwhile, to evaluate the effects on the behavior, larval fish at 6 days post-fertilization (dpf) were exposed to the same concentrations for 24 h. Here, we show that there are embryonic developmental defects, including abnormalities of head and trunk, brain ventricle atrophy, reduced newborn neurons, disordered neurons, increased intercellular space, concentrated cytoplasm, decreased heart beat and blood flow velocity, and developmental delay of the vascular system; in addition, some embryos exposed to the high concentration of OxCu degraded from the tail. We also found that the spontaneous tail coiling frequency and AChE enzyme activity were reduced, while oxidative stress (free radical damage) and cell apoptosis were significantly increased. Moreover, the expression of genes involved in neurodevelopment, vascular development and apoptosis were dysregulated in the OxCu exposed embryos in a concentration-dependent manner. Finally, we found that after exposure to OxCu, larval locomotor activity was decreased and accompanied by Parkinson-like (increased absolute turn angle and sinuosity) and anxiety-like (preferred to the central area) behavior. These results indicate that OxCu induces developmental toxicity and behavioral alterations by affecting AChE enzyme activity and oxidative stress. Our data present new proofs of OxCu toxicity and a warning for its application.