Abstract：
Fluopimomide is an innovative pesticide, widely used for agricultural pest management; however, little is known about its effect on non-target organisms. This study was designed to assess the potential risk of fluopimomide and the molecular mechanisms using Caenorhabditis elegans, a common model animal. The oxidative stress-related indicators were analyzed in C. elegans after exposure to fluopimomide for 24 h at three sublethal doses (0.2, 1.0, and 5.0 mg/L). The results demonstrated that sublethal exposure to fluopimomide adversely affected the nematodes growth, locomotive behaviors, reproduction, and lifespan, accompanying with enhanced of reactive oxygen species (ROS) generation, lipid and lipofuscin accumulation, and malondialdehyde content. In addition, exposure to fluopimomide significantly inhibited antioxidant systems including superoxide dismutase, catalase, glutathione S-transferase, and glutathione in the nematodes. Moreover, the expression of oxidative stress-related genes of sod-3, hsp-16.1, gst-4, ctl-2, daf-16, and daf-2 were significantly down-regulated, while the expression of skn-1 was significantly up-regulated. Further evidence revealed that daf-16 and skn-1 mutant strains of C. elegans significantly decreased ROS production upon fluopimomide exposure compared with the wild-type nematodes. Overall, our findings indicated that exposure to fluopimomide at sublethal doses caused oxidative damage, mainly associated with insulin/IGF-1-like signaling pathway in C. elegans. This is the first report of potential toxic effects of fluopimomide even at low concentrations, providing a new insight into the mechanisms of toxicity to C. elegans by fluopimomide.
摘要：
氟哌胺是一种创新的农药,广泛用于农业害虫管理；然而，对其对非靶标生物的影响知之甚少。本研究旨在评估氟哌胺的潜在风险和使用秀丽隐杆线虫的分子机制。一种常见的模型动物。在三种亚致死剂量（0.2、1.0和5.0mg/L）下暴露于氟哌米特24小时后，在秀丽隐杆线虫中分析了氧化应激相关指标。结果表明，亚致死暴露于氟哌米特对线虫的生长产生不利影响，机车行为，繁殖，和寿命，伴随着活性氧（ROS）生成的增强，脂质和脂褐素积累，和丙二醛含量。此外,暴露于氟哌米特显著抑制抗氧化系统，包括超氧化物歧化酶，过氧化氢酶,谷胱甘肽S-转移酶，和线虫中的谷胱甘肽。此外，sod-3、hsp-16.1、gst-4、ctl-2、daf-16和daf-2的氧化应激相关基因表达显著下调，而skn-1的表达显著上调。进一步的证据表明，与野生型线虫相比，秀丽隐杆线虫的daf-16和skn-1突变菌株在氟哌米特暴露后显着降低了ROS的产生。总的来说,我们的研究结果表明，暴露于亚致死剂量的氟哌米特会导致氧化损伤，主要与秀丽隐杆线虫胰岛素/IGF-1样信号通路有关。这是首次报道即使在低浓度下氟哌胺的潜在毒性作用,为氟哌米特对秀丽隐杆线虫的毒性机制提供了新的见解。
