Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.
Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.
Comp Biochem Physiol C Toxicol Pharmacol. 2023 Apr;266:109550. doi: 10.1016/j.cbpc.2023.109550. Epub 2023 Jan 28.
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.
重金属污染已成为严重的环境问题和公众健康威胁。三种最常见的重金属是镉（Cd）、铅（Pb）和锰（Mn）。核因子红细胞 2 相关因子 2（Nrf2）是一种在应对氧化应激时被激活的重要转录因子。在这项研究中，通过 CRISPR/Cas9 系统构建了 nrf2a 缺失 7 个碱基的突变斑马鱼，以研究这三种重金属的氧化毒性。一般毒性试验结果表明，与野生型（WT）斑马鱼相比，Pb 暴露并未对突变斑马鱼造成显著损伤。然而，高浓度 Mn 暴露会增加突变斑马鱼的死亡率和畸形率。值得关注的是，Cd 暴露会导致显著的毒性损伤，包括死亡率和畸形率增加、脑神经元凋亡以及突变斑马鱼严重的运动行为异常。qRT-PCR 结果表明，Cd 暴露可诱导 WT 斑马鱼中与抗氧化应激相关的基因激活，而这些基因在突变斑马鱼中的表达受到抑制。本研究表明，在这三种重金属中，Cd 的氧化毒性最强，Mn 的毒性居中，而 Pb 的毒性最弱。
