Developmental and cardiac toxicity assessment of Ethyl 3-(N-butylacetamido) propanoate (EBAAP) in zebrafish embryos.

Ethyl 3-(N-butylacetamido) propanoate (EBAAP) is one of the most widely used mosquito repellents worldwide, and is also commonly used to produce cosmetics. Residues have recently been detected in surface and groundwater in many countries, and their potential to harm the environment is unknown. Therefore, more studies are needed to fully assess the toxicity of EBAAP. This is the first investigation into the developmental toxicity and cardiotoxicity of EBAAP on zebrafish embryos. EBAAP was toxic to zebrafish, with a lethal concentration 50 (LC50) of 140 mg/L at 72 hours post fertilization (hpf). EBAAP exposure also reduced body length, slowed the yolk absorption rate, induced spinal curvature and pericardial edema, decreased heart rate, promoted linear lengthening of the heart, and diminished cardiac pumping ability. The expression of heart developmental-related genes (nkx2.5, myh6, tbx5a, vmhc, gata4, tbx2b) was dysregulated, intracellular oxidative stress increased significantly, the activities of catalase (CAT) and superoxide dismutase (SOD) decreased, and malondialdehyde (MDA) content increased significantly. The expression of apoptosis-related genes (bax/bcl2, p53, caspase9, caspase3) was significantly upregulated. In conclusion, EBAAP induced abnormal morphology and heart defects during the early stages of zebrafish embryo development by potentially inducing the generation and accumulation of reactive oxygen species (ROS) in vivo and activating the oxidative stress response. These events dysregulate the expression of several genes and activate endogenous apoptosis pathways, eventually leading to developmental disorders and heart defects.

Cardiac toxicity assessment of pendimethalin in zebrafish embryos.

Pendimethalin (PND) is one of the best sellers of selective herbicide in the world and has been frequently detected in the water. However, little is known about its effects on cardiac development. In this study, we used zebrafish to investigate the developmental and cardiac toxicity of PND. We exposed the zebrafish embryos with a serial of concentrations at 3, 4, and 5 mg/L at 5.5-72 h post-fertilization (hpf). We found that PND exposure can reduce the heart rate, survival rate, and body length of zebrafish embryos. Furthermore, we identified many malformations including pericardial and yolk sac edema, spinal deformity, and cardiac looping abnormality. In addition, PND increased the expression of reactive oxygen species and malondialdehyde and reduced the activity of superoxide dismutase (Antioxidant enzymes); We examined the expression of cardiac development-related genes and the apoptosis markers, and found changes of the following marker: vmhc, nppa, tbx5a, nkx2.5, gata4, tbx2b and FoxO1, bax, bcl-2, p53, casp-9, casp-3. Our data showed that activation of Wnt pathway can rescue the cardiac abnormalities caused by PND. Our results provided new evidence for the toxicity of PND and suggested that the PND residual should be treated as a hazard in the environment.