Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
J Hazard Mater. 2021 Jun 5;411:125153. doi: 10.1016/j.jhazmat.2021.125153. Epub 2021 Jan 14.
Pendimethalin, an herbicide used to control weeds, acts by inhibiting plant cell division and mitosis. Several studies have reported the detrimental effects of pendimethalin on non-target organisms. It has been found to be especially toxic to aquatic life. Additionally, there is some evidence that pendimethalin induces mitochondrial stress. However, none of the studies have provided information about the functional defects in mitochondria and toxicity during embryogenesis. In this study, we evaluated the impact of pendimethalin on the electron transport chain (ETC) activity and mitochondrial complexes via in vivo screening of oxidative phosphorylation and transcriptional profiles in zebrafish embryos. The results showed that pendimethalin interferes with mitochondrial complexes I and V, which inhibit embryo energy metabolism, thereby leading to developmental defects. Transgenic zebrafish, fli1:eGFP and olig2:dsRed, were used to confirm pendimethalin-induced functional depletion in neurogenesis and vasculogenesis during embryo development. This study provides new insights into the methodology of environmental assessment of biohazard chemicals that target ETC activity in mitochondria. Additionally, the results suggest that real-time respiratory and metabolic monitoring in zebrafish will be useful for the genotoxicity assessment of environmentally hazardous substances and may be used as an alternative model for the control of aquatic environmental pollutants.
二甲戊灵是一种用于控制杂草的除草剂，通过抑制植物细胞分裂和有丝分裂起作用。几项研究报告了二甲戊灵对非目标生物的有害影响。它被发现对水生生物尤其有毒。此外，有一些证据表明二甲戊灵诱导线粒体应激。然而，没有一项研究提供关于线粒体功能缺陷和胚胎发生期间毒性的信息。在这项研究中，我们通过体内筛选斑马鱼胚胎的氧化磷酸化和转录谱，评估了二甲戊灵对电子传递链（ETC）活性和线粒体复合物的影响。结果表明，二甲戊灵干扰线粒体复合物 I 和 V，抑制胚胎能量代谢，从而导致发育缺陷。使用 fli1:eGFP 和 olig2:dsRed 转基因斑马鱼来确认二甲戊灵在胚胎发育过程中对神经发生和血管发生的功能耗竭。这项研究为针对线粒体 ETC 活性的生物危害化学物质的环境评估方法提供了新的见解。此外，结果表明，在斑马鱼中进行实时呼吸和代谢监测将有助于对环境危害物质的遗传毒性评估，并可用作控制水生环境污染物的替代模型。
