Fetal and neonatal exposure to propofol can lead to neuronal death and long-term neurobehavioral deficiencies in both rodents and nonhuman primates. Zebrafish embryo, which is fertilized ex-utero, has provided us a new model species to study the effects of general anesthetics on developing brain. Inhibited electron transport chain leads to mitochondrial dysfunction and insufficient energy production. The aim of this study was to dissect the role of electron transport chain in propofol-induced neurotoxicity. 6 h post fertilization (hpf) zebrafish embryos were exposed to control or 1, 2 or 4 μg/ml propofol until 48hpf. Acridine orange staining was used to assess cell apoptosis in the brain of zebrafish embryos. The activity of mitochondrial electron transport chain complex was assessed using colorimetric method. Expression of key subunit of cytochrome c oxidase was assessed by western blot and transcription level of cox4i1 was assessed by quantitative real time-PCR. The mitochondrial membrane potential and ATP content were assessed. Exposure to 1, 2 and 4 μg/ml propofol induced significant increases in cell apoptosis in the brain of zebrafish embryos in a dose-dependent manner and led to significant decreases in electron transport chain complex IV activity from (0.161 ± 0.023)μmol/mg/min in blank control-treated group to (0.096 ± 0.015)μmol/mg/min, (0.083 ± 0.013)μmol/mg/min and (0.045 ± 0.014)μmol/mg/min respectively, accompanied by decreased expression of key regulatory subunit of cytochrome c oxidase-subunit IV and decreased transcription level of cox4i1. Propofol exposure also decreased the mitochondrial membrane potential and ATP content. Our findings demonstrate that inhibition of the electron transport chain is involved in the mechanisms by which propofol induces neurotoxicity in the developing brain.

中文翻译：

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丙泊酚中电子传输链的抑制引起斑马鱼胚胎中的神经毒性。

胎儿和新生儿暴露于丙泊酚可能导致啮齿动物和非人类灵长类动物神经元死亡和长期神经行为缺陷。宫外受精的斑马鱼胚胎为我们提供了一个新的模型物种，用于研究全身麻醉剂对大脑发育的影响。抑制的电子传输链导致线粒体功能障碍和能量产生不足。这项研究的目的是剖析电子传输链在异丙酚诱导的神经毒性中的作用。受精（hpf）后6小时，将斑马鱼胚胎暴露于对照或1、2或4μg/ ml异丙酚中直至48hpf。cr啶橙染色用于评估斑马鱼胚胎大脑中的细胞凋亡。使用比色法评估线粒体电子传输链复合物的活性。通过Western印迹评估细胞色素c氧化酶关键亚基的表达，并通过实时定量PCR评估cox4i1的转录水平。评估线粒体膜电位和ATP含量。暴露于1、2和4μg/ ml异丙酚可导致斑马鱼胚胎大脑中的细胞凋亡显着增加，且呈剂量依赖性，并导致电子传输链复合物IV活性从（0.161±0.023）μmol/ mg显着降低。空白对照组的/ min分别为（0.096±0.015）μmol/ mg / min，（0.083±0.013）μmol/ mg / min和（0.045±0.014）μmol/ mg / min亚基的细胞色素C氧化酶亚基IV和降低的转录水平cox4i1。异丙酚的暴露也降低了线粒体膜电位和ATP含量。