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.

中文翻译：

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亚致死剂量氟匹米胺暴露导致秀丽隐杆线虫氧化应激受胰岛素/胰岛素样生长因子1样信号通路调节

氟吡咪胺是一种创新农药，广泛用于农业病虫害防治；然而，人们对其对非目标生物的影响知之甚少。本研究旨在评估氟吡胺的潜在风险以及使用常见模型动物秀丽隐杆线虫的分子机制。在秀丽隐杆线虫中分析了氧化应激相关指标以三种亚致死剂量（0.2、1.0 和 5.0 mg/L）暴露于氟匹莫胺 24 小时后。结果表明，亚致死暴露于氟匹米胺对线虫的生长、运动行为、繁殖和寿命产生不利影响，同时增加了活性氧 (ROS) 的产生、脂质和脂褐质的积累以及丙二醛的含量。此外，暴露于氟匹莫胺显着抑制抗氧化系统，包括线虫中的超氧化物歧化酶、过氧化氢酶、谷胱甘肽 S-转移酶和谷胱甘肽。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的表达显着下调，而skn-1的表达显着上调。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突变株显着降低了暴露于氟匹莫胺后的 ROS 产生。总体而言，我们的研究结果表明，暴露于亚致死剂量的氟吡胺会导致氧化损伤，主要与秀丽隐杆线虫中的胰岛素/IGF-1 样信号通路有关。这是第一份关于氟吡胺潜在毒性作用的报告，即使在低浓度下也是如此，为氟吡胺对秀丽隐杆线虫的毒性机制提供了新的见解。