2,4,6-三氯苯甲醚(2,4,6-TCA),具有特有泥土气味的化合物,是饮用水和葡萄酒中气味污染物的常见来源。然而,对其生物毒性的研究是有限的。在这项研究中,我们使用斑马鱼作为指标模型来研究2,4,6-TCA暴露对形态发育的影响,氧化应激,凋亡,心率,血流量,和运动性。我们发现暴露于2,4,6-TCA会导致明显的脊髓,尾巴,和斑马鱼幼虫的心脏畸形,并促进了明显的氧化应激反应和广泛的细胞凋亡,尤其是在消化道,头部,脊柱,和心,最终导致斑马鱼心率显著降低,血流量,和运动性。此外,随着斑马鱼暴露的2,4,6-TCA浓度的增加,这些影响变得更加明显。此外,qPCR分析显示,暴露于2,4,6-TCA促进了与氧化应激相关的基因表达水平的显著变化,凋亡,心脏发育,和神经系统,特别是线粒体凋亡途径中的关键基因(p53,apaf1,casp9和casp3),显着上调。同样,我们检测到ache基因表达显著上调。这些发现表明,暴露于2,4,6-TCA导致斑马鱼中活性氧的积累,诱导强烈的氧化应激反应,并引发脂质过氧化和广泛的细胞凋亡。细胞凋亡,线粒体信号通路可以介导,已经发现会导致斑马鱼胚胎畸形,导致心脏功能和运动能力显著下降。据我们所知,这是对2,4,6-TCA毒性的首次系统评估,研究结果为2,4,6-TCA暴露的风险评估和预警提供了重要参考。
2,4,6-Trichloroanisole (2,4,6-TCA), a compound with a characteristic earthy odor, is a common source of odorous pollutants in drinking water and wine. However, research on its biological toxicity is limited. In this study, we used zebrafish as an indicator model to investigate the effects of 2,4,6-TCA exposure on morphological development, oxidative stress, apoptosis, heart rate, blood flow, and motility. We found that exposure to 2,4,6-TCA resulted in significant spinal, tail, and cardiac deformities in zebrafish larvae and promoted a pronounced oxidative stress response and extensive cell apoptosis, notably in the digestive tract, head, spine, and heart, ultimately leading to significant reductions in zebrafish heart rate, blood flow, and motility. Moreover, these effects became more pronounced with an increase in the concentration of 2,4,6-TCA to which the zebrafish were exposed. Furthermore, qPCR analysis revealed that exposure to 2,4,6-TCA promoted significant changes in the expression levels of genes associated with oxidative stress, apoptosis, cardiac development, and the nervous system, particularly key genes (p53, apaf1, casp9, and casp3) in the mitochondrial apoptotic pathway, which were significantly upregulated. Similarly, we detected significant upregulation of ache gene expression. These findings indicated that exposure to 2,4,6-TCA resulted in the accumulation of reactive oxygen species in zebrafish, induced strong oxidative stress responses, and triggered lipid peroxidation and extensive cell apoptosis. Cellular apoptosis, which mitochondrial signaling pathways may mediate, has been found to lead to malformations in zebrafish embryos, resulting in significant reductions in cardiac function and motility. To our knowledge, this is the first systematic assessment of the toxicity of 2,4,6-TCA, and our findings provide an important reference for risk assessment and early warning of 2,4,6-TCA exposure.