Development of a rapid zebrafish model for lead poisoning research and drugs screening

Abstract

Lead (Pb) contamination is a worldwide public health threaten. Besides close restraint of lead exposure, it's emergency to discover compounds that could help to cue toxicities caused by lead. Zebrafish embryos and early larvae can serve as valuable screening tools in early pre-clinical phase of drug screening and research. In order to establish a zebrafish lead poisoning model that could be used for drug screening and research, zebrafish embryos at 6 h post-fertilization (hpf) were treated with lead at different concentrations by soaking intermittently, raised in lead work solution at night while in fish water during the day. After treated for 90 h, death and severe trunk curvature were observed on zebrafish in 640 μM group, obvious dysplasia, blood toxicity, excessive reactive oxygen species (ROS), severe neurotoxicity, such as shorter length of peripheral motor neurons, neuronal apoptosis, and axonal injury, and neurobehavior impairment were induced by lead at 80, 160 and 320 μM, similar to phenotypes reported in rodent. Moreover, the mRNA level of genes related to neurodevelopment, memory, and antioxidation were significantly down regulated, and apoptosis-related genes were up regulated, consistent to zebrafish phenotypic change. Finally, zebrafish were intermittently exposed to 80 μM lead solution to establish the lead poisoning model, and the efficacy of a safe chelating agent Meso-2,3-Dimercaptosuccinic acid (DMSA) was tested at a series of concentrations to validate the zebrafish model. The result showed concentration-dependent decrease of lead content in zebrafish in DMSA treated groups compared with model group. The above data fully demonstrated a zebrafish model of lead poisoning suitable for drug screening was successfully developed, which was expected to provide a rapid and economic tools for discovering antidotes of lead and drugs of neuroprotection.