Protective effects of quercetin (QUE), polydatin (POL), and folic acid (FA) and their mixtures were tested using zebrafish to model fetal alcohol spectrum disorder in this study. Zebrafish embryos were exposed to 150 mM ethanol for 6 or 22 h and co-treated with QUE, POL, FA, and their mixtures (37.5–100.0 μM). Epiboly progression, teratogenic effects, and behavior were evaluated. Ethanol exposure reduced epiboly, and FA and QUE protected against these ethanol-induced defects. POL did not reduce epiboly defects. The mixture QUE + FA showed a possible antagonistic effect. The observed teratogenic effects were similar in all ethanol exposed groups. QUE, FA and QUE + POL reduced the percentage of affected animals, but treatments did not eliminate teratogenic effects. Behavioral measurements were divided into small (between 4 and 8 mm/s) and high swimming activity (>8 mm/s). All experimental groups displayed a reduction in small swimming activity as compared to control and ethanol groups when exposed to bright light. Additionally, larvae exposed to ethanol were more inhibited than control, not showing a habituation period (after 60 min of experiment) in high swimming activity. Chemical treatments like QUE and POL reduced behavioral defects induced by ethanol exposure. In conclusion, this study presents new evidence that QUE, POL, FA and their mixtures partially protected epiboly, teratogenic, and behavioral defects induced by ethanol exposure. QUE, FA and QUE + POL were more effective in reducing these defects than the other studied compounds and mixtures.

本研究使用斑马鱼模拟胎儿酒精谱系障碍，测试了槲皮素 (QUE)、虎杖甙 (POL) 和叶酸 (FA) 及其混合物的保护作用。将斑马鱼胚胎暴露于 150 mM 乙醇 6 或 22 小时，并与 QUE、POL、FA 及其混合物 (37.5–100.0 μM) 共同处理。对 Epiboly 进展、致畸作用和行为进行了评估。乙醇暴露减少了外聚，FA 和 QUE 可以防止这些乙醇引起的缺陷。POL 没有减少外延缺陷。混合物 QUE + FA 显示出可能的拮抗作用。在所有乙醇暴露组中观察到的致畸作用相似。QUE、FA 和 QUE + POL 降低了受影响动物的百分比，但治疗并没有消除致畸作用。行为测量分为小游泳活动（4 至 8 毫米/秒）和高游泳活动（> 8 毫米/秒）。当暴露在强光下时，与对照组和乙醇组相比，所有实验组的小规模游泳活动均有所减少。此外，接触乙醇的幼虫比对照受到更多抑制，在高游泳活动中没有表现出习惯期（实验 60 分钟后）。QUE 和 POL 等化学处理可减少乙醇暴露引起的行为缺陷。总之，这项研究提供了新的证据，表明 QUE、POL、FA 及其混合物部分保护了乙醇暴露引起的外胚层畸形、致畸和行为缺陷。QUE、FA 和 QUE + POL 在减少这些缺陷方面比其他研究的化合物和混合物更有效。