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.
Environ Res. 2020 Jun;185:109432. doi: 10.1016/j.envres.2020.109432. Epub 2020 Mar 28.
As a type of cyanobacterial toxins, saxitoxin (STX) is receiving great interest due to its increasing presence in waterbodies. However, the underlying mechanism of STX-induced adverse effect is poorly understood. Here, we examined the developmental toxicity and molecular mechanism induced by STX using zebrafish embryos as an animal model. The embryonic toxicity induced by STX was demonstrated by inhibition of embryo hatching, increase in mortality rate, abnormal heart rate, abnormalities in embryo morphology as well as defects in angiogenesis and common cardinal vein remodeling. STX induced embryonic DNA damage and cell apoptosis, which would be alleviated by antioxidant N-acetyl-L-cysteine. Additionally, STX significantly increased reactive oxygen species level, catalase activity and malondialdehyde content and decreased the activity of superoxide dismutase and glutathione content. STX also promoted the expression of vascular development-related genes DLL4 and VEGFC, and inhibited VEGFA expression. Furthermore, STX altered the transcriptional regulation of apoptosis-related genes (BAX, BCL-2, P53 and CASPASE 3). Taken together, STX induced adverse effect on development of zebrafish embryos, which might be associated with oxidative stress-induced apoptosis.
作为一种蓝藻毒素，石房蛤毒素（STX）因其在水体中的存在日益增加而受到广泛关注。然而，STX 诱导的不良反应的潜在机制尚不清楚。在这里，我们使用斑马鱼胚胎作为动物模型，研究了 STX 诱导的发育毒性和分子机制。STX 抑制胚胎孵化、增加死亡率、心率异常、胚胎形态异常以及血管生成和共同心静脉重塑缺陷，证明了 STX 诱导的胚胎毒性。STX 诱导胚胎 DNA 损伤和细胞凋亡，抗氧化剂 N-乙酰-L-半胱氨酸可减轻这种损伤。此外，STX 显著增加活性氧水平、过氧化氢酶活性和丙二醛含量，降低超氧化物歧化酶活性和谷胱甘肽含量。STX 还促进了血管发育相关基因 DLL4 和 VEGFC 的表达，并抑制了 VEGFA 的表达。此外，STX 改变了凋亡相关基因（BAX、BCL-2、P53 和 CASPASE 3）的转录调控。综上所述，STX 对斑马鱼胚胎发育产生了不良影响，这可能与氧化应激诱导的细胞凋亡有关。
