Ethanol- and acetaldehyde-mediated developmental toxicity in zebrafish
Ethanol- and acetaldehyde-mediated developmental toxicity in zebrafish
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DOI：
10.1016/j.ntt.2004.06.012
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发表时间：
2004-11-01
影响因子：
2.9
通讯作者：
Tanguay, RL
中科院分区：
文献类型：
--
作者：
Reimers, MJ;Flockton, AR;Tanguay, RL
乙醇是一种公认的发育毒物；然而，这种毒性的机制(S)仍不清楚。斑马鱼正成为评价化学和药物毒性的重要模型系统。在这项研究中，斑马鱼胚胎被用来比较乙醇和乙醛暴露引起的发育毒性。胚胎暴露在水基乙醇浓度下的时间长短不一，但涵盖了胚胎发育的最早阶段。在45小时酒精暴露后，导致50%死亡率的水基乙醇浓度约为340 mM(1.98%v/v)。酒精暴露导致了许多可复制的终点，包括心包水肿、卵黄囊水肿、轴心畸形、耳石缺陷、发育迟缓和轴心起泡。当暴露时间缩短时，在几乎相同的乙醇浓度下也会产生类似的毒性迹象。为了估计特定水基乙醇浓度下的胚胎剂量，采用了动态酒精脱氢酶(ADH)检测方法。胚胎酒精的平均剂量被计算为水中浓度的一小部分。暴露在水性乙醛中的胚胎产生的终点与乙醇诱导的终点相似，但不完全相同。然而，胚胎对乙醛的敏感度几乎比对乙醇的敏感度高三个数量级。乙醇和乙醛都对胚胎发育有负面影响；然而，根据致畸指数(TIS)，乙醇的致畸作用更强。这些结果表明，斑马鱼模型将为进一步评估乙醇对脊椎动物发育的作用机制提供机会。(C)2004 Elsevier Inc.保留所有权利。
Ethanol is a well-established developmental toxicant; however, the mechanism(s) of this toxicity remains unclear. Zebrafish are becoming an important model system for the evaluation of chemical and drug toxicity. In this study, zebrafish embryos were utilized to compare the developmental toxicity resulting from either ethanol or acetaldehyde exposure. Embryos were exposed to waterborne ethanol concentrations for various lengths of time but encompassed the earliest stages of embryogenesis. The waterborne ethanol concentration that causes 50% mortality (LC50) following a 45-h ethanol exposure was approximately 340 mM (1.98% v/v). A number of reproducible endpoints resulted from ethanol exposure and included pericardial edema, yolk sac edema, axial malformations, otolith defects, delayed development, and axial blistering. When the exposure period was reduced, similar signs of toxicity were produced at nearly identical ethanol concentrations. To estimate the embryonic dose following a given waterborne ethanol concentration, a kinetic alcohol dehydrogenase (ADH) assay was adapted. The average embryonic ethanol dose was calculated to be a fraction of the waterborne concentration. Embryos exposed to waterborne acetaldehyde resulted in similar, but not identical, endpoints as those induced by ethanol. Embryos were however, almost three orders of magnitude more sensitive to acetaldehyde than to ethanol. Ethanol and acetaldehyde both negatively impact embryonic development; however, ethanol is more teratogenic based on teratogenic indices (TIs). These results demonstrate that the zebrafish model will provide an opportunity to further evaluate the mechanism of action of ethanol on vertebrate development. (C) 2004 Elsevier Inc. All rights reserved.