The toxic effect of Amiodarone on valve formation in the developing heart of zebrafish embryos

Chen, Ying Hsin; Lee, Hung Chieh; Hsu, Ren Jun; Chen, Ta Yuan; Huang, Yu; Lo, Hao‐Yung; Hu, Sheng; Harn, Horng Jyh; Jeng, Jing-Ren; Sun, Chi‐Kuang; Lin, Shinn Zong; Tsai, Huai Jen

doi:10.1016/j.reprotox.2011.12.008

Cited by 18 publications

(17 citation statements)

References 32 publications

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“…Acetaminophen is known to cause tail, heart and yolk sac malformations [ 15 , 16 ], while propanolol exposure leads to large pericardial edema, weakened pigmentation and tail curvatures [ 17 ]. Finally, amiodarone is known to cause failure of cardiac valve formation in zebrafish embryos [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

Phenotype Classification of Zebrafish Embryos by Supervised Learning

et al. 2015

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Zebrafish is increasingly used to assess biological properties of chemical substances and thus is becoming a specific tool for toxicological and pharmacological studies. The effects of chemical substances on embryo survival and development are generally evaluated manually through microscopic observation by an expert and documented by several typical photographs. Here, we present a methodology to automatically classify brightfield images of wildtype zebrafish embryos according to their defects by using an image analysis approach based on supervised machine learning. We show that, compared to manual classification, automatic classification results in 90 to 100% agreement with consensus voting of biological experts in nine out of eleven considered defects in 3 days old zebrafish larvae. Automation of the analysis and classification of zebrafish embryo pictures reduces the workload and time required for the biological expert and increases the reproducibility and objectivity of this classification.

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Section: Resultsmentioning

confidence: 99%

Phenotype Classification of Zebrafish Embryos by Supervised Learning

et al. 2015

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“…Treatment of zebrafish embryos with Amiodarone, an anti-arrhythmia drug, caused a massive ectopic upregulation of versican in the atrium, the ventricle and the AV canal and resulted in a loss of endocardial cushion formation in developing embryos that was restored by morpholino-mediated knockdown of versican (Chen et al, 2012). This suggested that tight regulation of versican expression was crucial for normal heart development.…”

Section: Major Developmental Contexts and Functions For Versicanmentioning

confidence: 99%

The multiple, complex roles of versican and its proteolytic turnover by ADAMTS proteases during embryogenesis

2014

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Embryonic development is an exceptionally dynamic process, requiring a provisional extracellular matrix that is amenable to rapid remodeling, and proteolytic or non-proteolytic mechanisms that can remodel the major components of this matrix. Versican is a chondroitin-sulfate proteoglycan that forms highly hydrated complexes with hyaluronan and is widely distributed in the provisional matrix of mammalian embryos. It has been extensively studied in the context of cardiovascular morphogenesis, neural crest cell migration and skeletal development. Analysis of Vcan transgenic mice has established the requirement for versican in cardiac development and its role in skeletogenesis. The ADAMTS family includes several versican-degrading proteases that are active during remodeling of the embryonic provisional matrix, especially during sculpting of versican-rich tissues. Versican is cleaved at specific peptide bonds by ADAMTS proteases, and the cleavage products are detectable by neo-epitope antibodies. Myocardial compaction, closure of the secondary palate (in which neural crest derived cells participate), endocardial cushion remodeling, myogenesis and interdigital web regression are developmental contexts in which ADAMTS-mediated versican proteolysis has been identified as a crucial requirement. ADAMTS proteases are expressed coordinately and function cooperatively in many of these contexts. In addition to versican clearance, ADAMTS proteases generate a bioactive versican fragment containing the N-terminal G1 domain, which we have named versikine. This review promotes the view that the embryonic extracellular matrix has evolved not only to provide a permissive environment for embryo growth and morphogenesis, but through its dissolution to influence and regulate cellular processes.

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“…Similarities of drug metabolism systems, genetics and pharmacology between zebrafish and mammals have prompted using zebrafish to study drug metabolism, pharmacology and toxicology (Li et al, 2010;Scholz, 2012;Takaki et al, 2012). Recently, abundant chemical and drug toxicity screening have been conducted using zebrafish embryos (Chen et al, 2012;Mathias et al, 2012;Peterson and Fishman, 2011). Relevance and predictability of drug response between zebrafish and human have been studied, and it has been found that zebrafish show a high percentage of predictability (78% and 70%) of drug response (Hung et al, 2012;Sukardi et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Cardiotoxicity evaluation of anthracyclines in zebrafish (Danio rerio)

Han

Zhang

Qian

et al. 2014

J of Applied Toxicology

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Drug-induced cardiotoxicity is a leading factor for drug withdrawals, and limits drug efficacy and clinical use. Therefore, new alternative animal models and methods for drug safety evaluation have been given great attention. Anthracyclines (ANTs) are widely prescribed anticancer agents that have a cumulative dose relationship with cardiotoxicity. We performed experiments to study the toxicity of ANTs in early developing zebrafish embryos, especially their effects on the heart. LC50 values for daunorubicin, pirarubicin, doxorubicin (DOX), epirubicin and DOX-liposome at 72 h post-fertilization were 122.7 μM, 111.9 μM, 31.2 μM, 108.3 μM and 55.8 μM, respectively. At the same time, zebrafish embryos were exposed to ANTs in three exposure stages and induced incomplete looping of the heart tube, pericardia edema and bradycardia in a dose-dependent manner, eventually leading to death. DOX caused the greatest heart defects in the treatment stages and its liposome reduced the effects on the heart, while daunorubicin produced the least toxicity. Genes and proteins related to heart development were also identified to be sensitive to ANT exposure and downregulated by ANTs. It revealed ANTs could disturb the heart formation and development. ANTs induced cardiotoxicity in zebrafish has similar effects in mammalian models, indicating that zebrafish may have a potential value for assessment of drug-induced developmental cardiotoxicity.

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The toxic effect of Amiodarone on valve formation in the developing heart of zebrafish embryos

Cited by 18 publications

References 32 publications

Phenotype Classification of Zebrafish Embryos by Supervised Learning

Phenotype Classification of Zebrafish Embryos by Supervised Learning

The multiple, complex roles of versican and its proteolytic turnover by ADAMTS proteases during embryogenesis

Cardiotoxicity evaluation of anthracyclines in zebrafish (Danio rerio)

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