Abstract：
The simultaneous or sequential application of pesticides such as triazophos (TRI) and fenvalerate (FEN) in agriculture results in their residues co-existing in the environments. However, the impact of co-exposure to TRI and FEN on the gut-liver axis, along with the underlying mechanisms, remains unclear. Our results showed that exposure to FEN (96 h-LC50 value of 0.096 mg a.i. L-1) was more toxic to adult zebrafish compared to TRI (96 h-LC50 value of 6.75 mg a.i. L-1). Furthermore, the study aimed to reveal the toxic potencies of individual and combined exposure to TRI and FEN on the liver-gut axis in zebrafish (Danio rerio). Our results also indicated that pesticide exposure decreased tight junction molecule expression and increased intestinal inflammatory molecule expression in D. rerio, with co-exposure demonstrating enhanced toxicity. Co-exposure altered gut flora structure and species abundance. RNA-Seq sequencing revealed changes in liver gene expressions, particularly enrichment of P53 signaling. Molecular docking demonstrated FEN\'s stronger binding to P53 and Caspase3, correlating with its higher toxicity. Liver pathology confirmed exacerbated liver damage by individual and co-exposures, with co-exposure inducing more severe liver injury. qPCR results showed increased pro-apoptotic gene expression and decreased anti-apoptotic gene expression, with co-exposure exhibiting an interactive effect. Overall, this study identifies specific targets and pathways influenced by these pesticides, revealing toxicity mechanisms involving the gut-liver axis, which is crucial for environmental risk assessment of pesticide mixtures.
摘要：
农药如三唑磷(TRI)和氰戊菊酯(FEN)在农业中的同时或顺序施用导致它们的残留物在环境中共存。然而,共同暴露于TRI和FEN对肠-肝轴的影响，以及潜在的机制，尚不清楚。我们的结果表明，与TRI（96h-LC50值为6.75mga.i.L-1）相比，暴露于FEN（96h-LC50值为0.096mga.i.L-1）对成年斑马鱼的毒性更大。此外，该研究旨在揭示斑马鱼（Daniorerio）在肝-肠轴上单独和联合暴露于TRI和FEN的毒性效应。我们的研究结果还表明，农药暴露降低了D.rerio的紧密连接分子表达和增加肠道炎症分子表达，共同暴露表明毒性增强。共同暴露改变了肠道菌群结构和物种丰度。RNA-Seq测序显示肝脏基因表达的变化，特别是P53信号的富集。分子对接表明FEN与P53和Caspase3的结合更强，与其较高的毒性相关。肝脏病理证实，个体和共同暴露加剧了肝脏损伤，共同暴露诱导更严重的肝损伤。qPCR结果显示促凋亡基因表达增加，抗凋亡基因表达减少，共同曝光表现出互动效果。总的来说,这项研究确定了受这些农药影响的特定靶标和途径，揭示涉及肠-肝轴的毒性机制，这对于农药混合物的环境风险评估至关重要。
