Ethanol- and acetaldehyde-mediated developmental toxicity in zebrafish.

TitleEthanol- and acetaldehyde-mediated developmental toxicity in zebrafish.
Publication TypeJournal Article
Year of Publication2004
AuthorsReimers, MJ, Flockton, AR, Tanguay, RL
JournalNeurotoxicol Teratol
Date Published2004 Nov-Dec
KeywordsAbnormalities, Multiple, Acetaldehyde, Alcohol Dehydrogenase, Animals, Biological Assay, Bone and Bones, Disease Models, Animal, Dose-Response Relationship, Drug, Ear, Inner, Edema, Embryo, Nonmammalian, Ethanol, Female, Pericardium, Survival Rate, Teratogens, Yolk Sac, Zebrafish

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 (LC(50)) 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.

Alternate JournalNeurotoxicol Teratol
PubMed ID15451041
Grant ListES00210 / ES / NIEHS NIH HHS / United States
R21 AA012783 / AA / NIAAA NIH HHS / United States
ES03850 / ES / NIEHS NIH HHS / United States
AA12783 / AA / NIAAA NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States