School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211800, China.
School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211800, China.
Aquat Toxicol. 2022 Jul;248:106195. doi: 10.1016/j.aquatox.2022.106195. Epub 2022 May 13.
Zinc pyrithione (ZPT) is a frequently used organometallic biocide, carrying potentially adverse consequences to multiple species in the environment. Previously we have demonstrated its embryonic, organ developmental and liver metabolic toxicity of zebrafish. However, details of ZPT toxicity during embryogenesis are still limited. The present study was designed to evaluate the effects and possible mechanisms of ZPT-induced embryonic toxicogenomic responses by morphological investigations, transcriptome and gene quantitative analysis, as well as biochemical assays. The results revealed that treatment with ZPT caused embryogenesis toxicity, specifically in irregular cell division and rearrangement, delayed differentiations of eyes and notochords, the epiboly and germ ring formation and somite segmentation defects. In addition, ZPT exposure altered gene expression during early embryonic development, especially related with morphological abnormities and metabolic dysfunctions including reduction of oxidoreductase activity. Activities of antioxidants and caspases examinations showed inductions of oxidative stress and apoptosis by ZPT and quantitative analysis of marker genes further indicated that ZPT also triggered endoplasmic reticulum (ER) stress and autophagy. Thus, we deduce here that ZPT-induced embryonic toxicogenomic responses reveal involvement of oxidative damage, apoptosis, endoplasmic reticulum (ER) stress and autophagy.
吡啶硫酮锌(ZPT)是一种常用的有机金属杀生物剂,对环境中的多种物种可能产生不利影响。此前,我们已经证明了其对斑马鱼的胚胎、器官发育和肝脏代谢毒性。然而,ZPT 在胚胎发生过程中的毒性细节仍然有限。本研究旨在通过形态学研究、转录组和基因定量分析以及生化分析来评估 ZPT 诱导的胚胎毒代基因组反应的影响和可能的机制。结果表明,ZPT 处理导致胚胎发生毒性,特别是在细胞分裂和排列不规则、眼睛和脊索的分化延迟、胚环和胚环形成以及体节分割缺陷。此外,ZPT 暴露改变了早期胚胎发育过程中的基因表达,特别是与形态异常和代谢功能障碍相关的基因表达,包括氧化还原酶活性降低。抗氧化剂和半胱天冬酶活性的检测表明 ZPT 诱导了氧化应激和细胞凋亡,标记基因的定量分析进一步表明 ZPT 还触发了内质网(ER)应激和自噬。因此,我们推断 ZPT 诱导的胚胎毒代基因组反应涉及氧化损伤、细胞凋亡、内质网(ER)应激和自噬。