Journal
JOURNAL OF APPLIED TOXICOLOGY
Volume 33, Issue 6, Pages 466-470Publisher
WILEY-BLACKWELL
DOI: 10.1002/jat.1768
Keywords
zebrafish; cardiotoxicity; atypical antipsychotic drug; LC50; heart beat rate
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Funding
- BioGreen 21 Program [20070401034031]
- Cooperative Research Program for Agriculture Science and Technology Development of the Rural Development Administration, Republic of Korea [PJ00779306]
- National Research Foundation of Korea (NRF)
- Korean government (MEST) [2010-0022263]
- National Research Foundation of Korea [2010-0022263] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- Rural Development Administration (RDA), Republic of Korea [20070401034031] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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The zebrafish model has been developed and evaluated for its ability to predict the toxicity of chemicals. Zebrafish additionally serve as an excellent model for assessing drug-induced cardiotoxicity, although zebrafish and mammalian hearts differ in structure. Recently, regulatory authorities have expressed concerns about a possible relationship between antipsychotics and risk of QTc interval prolongation, serious arrhythmia and sudden cardiac death. In the current study, we performed a cardiovascular risk assessment of six atypical antipsychotic drugs in zebrafish, specifically, aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone. Visual endpoints, such as lethality, edema (the presence of heart and trunk edema), hemorrhage (clustering of a pool of blood in an area outside the normal circulation), abnormal body shape (including bent or misshapen caudal region of the larvae) and motility, were evaluated as general toxicity endpoints, and the heart beat rate calculated as the cardiovascular toxicity endpoint. The zebrafish model facilitates determination of the heart beat rate, and may thus be an attractive screening tool for cardiovascular risk assessment of atypical antipsychotic drugs to understand the variations in response to QT-prolonging drugs. Copyright (c) 2011 John Wiley & Sons, Ltd.
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