Low trifloxystrobin-tebuconazole concentrations induce cardiac and developmental toxicity in zebrafish by regulating notch mediated-oxidative stress generation

Trifloxystrobin-tebuconazole (TFS-TBZ) is a novel, broad-spectrum fungicide that has been frequently detected in both the environment and agricultural products. However, its adverse effects on aquatic organisms remain unknown. In this study, the adverse effects of ecologically relevant TFS-TBZ concentrations (i.e., 75.0, 112.5, and 150.0 μg/L) on the heart and development of zebrafish were investigated. TFS-TBZ was found to substantially hinder development, inhibit growth, and cause significant abnormity at higher concentrations. Moreover, TFS-TBZ caused severe pericardial edema, heart loop failure, cardiac linearization, and ultra-slow heartbeat, implying that TFS-TBZ might induce congenital heart disease. TFS-TBZ inhibited Notch signaling and increased the intracellular generation of Reactive Oxygen Species, resulting in decreased myocardial cell proliferation and increased Apoptosis. The use of sodium valproate and Gadofullerene illustrated the relevance of the Notch signaling system and oxidative stress. Finally, TFS-TBZ exposure conveys severe developmental toxicity to the zebrafish heart. The underlying mechanism is regulation Notch mediated-oxidative stress generation, implying that TFS-TBZ may be potentially hazardous to aquatic organisms in the environment.