Thiobencarb induces phenotypic abnormalities, apoptosis, and cardiovascular toxicity in zebrafish embryos through oxidative stress and inflammation

Thiobencarb is a representative herbicide used on rice paddies. Because thiobencarb is used extensively on agricultural lands, especially on paddy fields, there is a high risk of unintended leaks into aquatic ecosystems. For this reason, several studies have investigated and reported on the toxicity of thiobencarb to aquatic species. In European eels, thiobencarb affected acetylcholinesterase levels in plasma and impaired adenosine triphosphatase activity in their gills. In medaka, thiobencarb-exposed embryos showed lower viability. However, molecular mechanisms underlying thiobencarb-mediated embryotoxicity have yet to be clarified. Therefore, the objective of our study was to investigate its mechanism of toxicity using zebrafish embryos. The viability of zebrafish embryos decreased upon exposure to thiobencarb and various phenotypic abnormalities were observed at con-centrations lower than the lethal dose. The developmental toxicity of thiobencarb was mediated by pro-inflammatory cytokines (il1b, cxcl8, cxcl18b, and cox2a) and excessive generation of reactive oxygen species due to the downregulation of genes such as catalase, sod1, and sod2, which encode antioxidant enzymes. In addition, severe defects of the cardiovascular system were identified in response to thiobencarb exposure. Specifically, deformed cardiac looping, delayed common cardinal vein (CCV) regression, and interrupted dorsal aorta (DA)-posterior cardinal vein (PCV) segregation were observed. Our results provide an essential resource that demonstrates molecular mechanisms underlying the toxicity of thiobencarb on non-target organisms, which may contribute to the establishment of a mitigation strategy.

Automated summary

Thiobencarb, a widely used herbicide on rice paddies, has been found to have toxic effects on aquatic organisms. This study investigated the mechanism of toxicity in zebrafish embryos and found that thiobencarb caused decreased viability, phenotypic abnormalities, and defects in the cardiovascular system. The toxicity was mediated by pro-inflammatory cytokines and excessive reactive oxygen species generation due to the downregulation of antioxidant enzyme genes.