Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400030, China.
Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400030, China.
Ecotoxicol Environ Saf. 2020 May;194:110444. doi: 10.1016/j.ecoenv.2020.110444. Epub 2020 Mar 10.
Nodularin (NOD) is a kind of cyanobacterial toxins. It is of concern due to elicit severe genotoxicity in humans and animals. The comprehensive evaluation of NOD-induced adverse effects in living organisms is urgently needed. This study is aimed to report the developmental toxicity and molecular mechanism using zebrafish embryos exposed to NOD. The embryonic toxicity induced by NOD is demonstrated by inhibition of embryo hatching, increase in mortality rate, abnormal heart rate, embryonic malformation as well as defects in angiogenesis and common cardinal vein remodeling. NOD triggered a decreased rate of angiogenesis through inhibiting endothelial cells migration. NOD induced embryonic cell apoptosis and DNA damage, which can be alleviated by antioxidant N-acetyl-L-cysteine. NOD significantly caused oxidative damage as indicated by changes in reactive oxygen species, superoxide dismutase, catalase, glutathione and malondialdehyde. NOD also altered the expression of vascular development-genes (DLL4, CDH5, VEGFA, VEGFC) and apoptosis-related genes (BAX, BCL-2, P53, CASPASE 3). Taken together, NOD induced adverse effect on zebrafish embryos development, which may be associated with oxidative stress and apoptosis through the activation of P53-BAX/BCL-2-CASPASE 3-mediated pathway.
节球藻毒素（NOD）是一种蓝藻毒素。由于它会在人类和动物体内引发严重的遗传毒性，因此引起了人们的关注。迫切需要对 NOD 引起的生物体不良影响进行全面评估。本研究旨在通过暴露于 NOD 的斑马鱼胚胎报告其发育毒性和分子机制。NOD 诱导的胚胎毒性表现为胚胎孵化抑制、死亡率增加、心率异常、胚胎畸形以及血管生成和普通心静脉重塑缺陷。NOD 通过抑制内皮细胞迁移来触发血管生成减少。NOD 诱导胚胎细胞凋亡和 DNA 损伤，抗氧化剂 N-乙酰-L-半胱氨酸可减轻这种损伤。NOD 导致活性氧、超氧化物歧化酶、过氧化氢酶、谷胱甘肽和丙二醛的变化，表明其引起了氧化损伤。NOD 还改变了血管发育相关基因（DLL4、CDH5、VEGFA、VEGFC）和凋亡相关基因（BAX、BCL-2、P53、CASPASE 3）的表达。总之，NOD 对斑马鱼胚胎发育产生了不良影响，这可能与氧化应激和凋亡有关，其通过激活 P53-BAX/BCL-2-CASPASE 3 介导的途径。
