Abstract：
Alcohol, or ethanol, is a major contributor to detrimental diseases and comorbidities worldwide. Alcohol use during pregnancy intervenes the developing embryos leading to morphological changes, neurocognitive defects, and behavioral changes known as fetal alcohol spectrum disorder (FASD). Zebrafish have been used as a model to study FASD; however, the mechanism and the impact of ethanol on oxidative stress and inflammation in the zebrafish FASD model remain unexplored. Hence, we exposed zebrafish embryos to different concentrations of ethanol (0 %, 0.5 %, 1.0 %, 1.25 %, and 1.5 % ethanol (v/v)) at 4-96 hours post-fertilization (hpf) to study and characterize the ethanol concentration for the FASD model to induce oxidative stress and inflammation. Here, we studied the survival rate and developmental toxicity parameters at different time points and measured oxidative stress, reactive oxygen species (ROS) generation, apoptosis, and pro-inflammatory gene expression in zebrafish larvae. Our findings indicate that ethanol causes various developmental abnormalities, including decreased survival rate, spontaneous tail coiling, hatching rate, heart rate, and body length, associated with increased malformation. Further, ethanol exposure induced oxidative stress by increasing lipid peroxidation and nitric oxide production and decreasing glutathione levels. Subsequently, ethanol increased ROS generation, apoptosis, and pro-inflammatory gene (TNF-α and IL-1β) expression in ethanol exposed larvae. 1.25 % and 1.5 % ethanol had significant impacts on zebrafish larvae in all studied parameters. However, 1.5 % ethanol showed decreased survival rate and increased malformations. Overall, 1.25 % ethanol is the ideal concentration to study the oxidative stress and inflammation in the zebrafish FASD model.
摘要：
酒精,或乙醇，是全球有害疾病和合并症的主要贡献者。怀孕期间使用酒精会干预发育中的胚胎，导致形态变化，神经认知缺陷，以及称为胎儿酒精谱系障碍（FASD）的行为变化。斑马鱼已被用作研究FASD的模型；然而，在斑马鱼FASD模型中，乙醇对氧化应激和炎症的作用机制和影响仍未被研究。因此，我们将斑马鱼胚胎暴露于不同浓度的乙醇(0%，0.5%,1.0%，1.25%,和1.5％乙醇（v/v））在受精后4-96小时（hpf）研究和表征FASD模型诱导氧化应激和炎症的乙醇浓度。这里,我们研究了不同时间点的存活率和发育毒性参数，并测量了氧化应激，活性氧（ROS）的产生，凋亡，斑马鱼幼虫的促炎基因表达。我们的发现表明，乙醇会导致各种发育异常，包括存活率下降，自发的尾部盘绕，孵化率,心率,和身体长度，与畸形增加有关。Further,乙醇暴露通过增加脂质过氧化和一氧化氮的产生以及降低谷胱甘肽水平来诱导氧化应激。随后，乙醇增加了ROS的产生，凋亡，乙醇暴露幼虫的促炎基因（TNF-α和IL-1β）表达。在所有研究参数中，1.25％和1.5％的乙醇对斑马鱼幼虫都有显着影响。然而,1.5%乙醇显示存活率降低和畸形增加。总的来说,1.25%乙醇是研究斑马鱼FASD模型氧化应激和炎症反应的理想浓度。
