Evaluation of the oxidative toxicity induced by lead, manganese, and cadmium using genetically modified nrf2a-mutant zebrafish

Heavy metal pollution has become a serious environmental concern and a threat to public health. Three of the most common heavy metals are cadmium (Cd), lead (Pb), and manganese (Mn). Nuclear factor erythroid 2–related factor 2 (Nrf2) is an important transcription factor activated in the response to oxidative stress. In this study, mutant zebrafish with an nrf2a deletion of 7 bp were constructed by the CRISPR/Cas9 system to investigate the oxidative toxicity of these three heavy metals. The results of general toxicity tests showed that Pb exposure did not cause significant damage to mutant zebrafish compared with wild-type (WT) zebrafish. However, high Mn exposure increased mortality and malformation rates in mutant zebrafish. Of concern, Cd exposure caused significant toxic damage, including increased mortality and malformation rates, apoptosis of brain neurons, and severe locomotor behavior aberration in mutant zebrafish. The results of qRT-PCR indicated that Cd exposure could induce the activation of genes related to oxidative stress resistance in WT zebrafish, while the expression of these genes was inhibited in mutant zebrafish. This study showed that of the three heavy metals, Cd had the strongest oxidative toxicity, Mn had medium toxicity, and Pb had the weakest toxicity.