제브라피쉬를 이용한 티람의 혈관신생 억제 및 발달독성 평가

Evaluation of the Angiogenesis Inhibition and Developmental Toxicity of Thiram Using Zebrafish

Background: Thiram has been widely used to prevent fungal diseases in crops, as a vulcanization accelerator, and as a component in sunscreens. Excessive use of this chemical has led to its detection in water, sediment, and soil. However, its developmental toxicity and the underlying mechanisms in aquatic organisms remain poorly understood. Objectives: In this study, the effects of thiram on the development and angiogenesis inhibition of zebrafish larvae were investigated. Methods: Zebrafish embryos were exposed to control, solvent control, and thiram (0.03, 0.1, 0.3, 1, 3, and 10 μg/L) for 96 hours. Developmental deformities, hatching rates, and mortality were checked every 24 hours. The expression of genes related to angiogenesis (e.g., endoglin (eng ), soluble fms-like tyrosine kinase 1 (sflt-1), and vascular endothelial growth factor Aa (vegfaa)) along with changes in VEGF was measured to elucidate the mechanism of developmental toxicity. Results: In embryos/larvae exposed to thiram, an increase in abnormal somites, abnormal eye pigmentation, abnormal tail morphology, pericardial edema, and yolk sac edema were all observed. In particular, delayed hatching was significantly increased in the concentration group of 0.3 μg/L or higher. In addition, eng and sflt-1 genes were significantly increased, and VEGF and vegfaa gene expression was significantly decreased, confirming that thiram inhibits angiogenesis. Conclusions: Our observations suggest that exposure to thiram may impair angiogenesis, ultimately resulting in developmental toxicity.