Exposure to fluopimomide at sublethal doses causes oxidative stress in Caenorhabditis elegans regulated by insulin/insulin-like growth factor 1-like signaling pathway.

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 5.0mg/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.