Zebrafish developmental screening of the ToxCast™ Phase I chemical library

Padilla, Stephanie; Corum, Daniel; Padnos, Beth; Hunter, Deborah L.; Beam, Andrew L.; Houck, Keith A.; Sipes, Nisha S.; Kleinstreuer, Nicole; Knudsen, Thomas B.; Dix, David J.; Reif, David M.

doi:10.1016/j.reprotox.2011.10.018

Cited by 289 publications

(286 citation statements)

References 75 publications

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“…The red-shift of λEm of ICG in the presence of BSA was consistent with a previous study. 27,28 Consistent with this, in vivo fluorescent imaging using CLSM of zebrafish stained with EB (100 μM) or ICG (100 μM) by static immersion failed to visualize the CBV (data not shown). We then administered these dyes into zebrafish by intracardiac injection.…”

Section: ■ Results and Discussionsupporting

confidence: 53%

Identification of a Novel Indoline Derivative for in Vivo Fluorescent Imaging of Blood-Brain Barrier Disruption in Animal Models

Nishimura

Yata

Nomoto

et al. 2013

ACS Chem. Neurosci.

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Disruption of the blood-brain barrier (BBB) can occur in various pathophysiological conditions. Administration of extraneous tracers that can pass the disrupted, but not the intact, BBB and detection of the extravasation have been widely used to assess BBB disruption in animal models. Although several fluorescent tracers have been successfully used, the administration of these tracers basically requires intravascular injection, which can be laborious when using small animals such as zebrafish. To identify fluorescent tracers that could be easily administered into various animal models and visualize the BBB disruption in vivo, we prepared nine structurally related indoline derivatives (IDs) as a minimum set of diverse fluorescent compounds. We found that one ID, ZMB741, had the highest affinity for serum albumin and emitted the strongest fluorescence in the presence of serum albumin of the nine IDs tested. The affinity to serum albumin and the fluorescence intensity was superior to those of Evans blue and indocyanine green that have been conventionally used to assess the BBB disruption. We showed that ZMB741 could be administered into zebrafish by static immersion or mice by intraperitoneal injection and visualizes the active disruption of their BBB. These results suggest that ZMB741 can be a convenient and versatile tool for in vivo fluorescent imaging of BBB disruption in various animal models. The strategy used in this study can also be applied to diversity-oriented libraries to identify novel fluorescent tracers that may be superior to ZMB741.

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Section: ■ Results and Discussionsupporting

confidence: 53%

Identification of a Novel Indoline Derivative for in Vivo Fluorescent Imaging of Blood-Brain Barrier Disruption in Animal Models

Nishimura

Yata

Nomoto

et al. 2013

ACS Chem. Neurosci.

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“…Efforts are underway to combine the use of iPSC models along with high-throughput screening assays using reporter gene assays [82], 3D organotypic cultures [94], human on a chip (www.ncats.nih.gov/research/reengineering/tissue-chip/ tissue-chip.html), and complementary animal models such as zebrafish [95,96] and C. elegans [97], and to incorporate human dosimetry and exposure to better predict toxicity across different organ systems [98]. As these multiple assay domains are being populated with data from the testing of chemicals, they are being anchored to relevant phenotypes from in vivo rodent and nonrodent animal studies as found in the EPA ToxRefDB [85,99], the NTP rodent database (CEBS) (www.niehs.nih.gov/research/resources/databases/ cebs), and whenever possible to the relevant phenotype in humans to develop better prediction models of toxicity.…”

Section: Toxicology In the 21st Centurymentioning

confidence: 99%

Induced Pluripotent Stem Cell Models to Enable In Vitro Models for Screening in the Central Nervous System

Hunsberger

Efthymiou

Malik

et al. 2015

Stem Cells and Development

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There is great need to develop more predictive drug discovery tools to identify new therapies to treat diseases of the central nervous system (CNS). Current nonpluripotent stem cell-based models often utilize non-CNS immortalized cell lines and do not enable the development of personalized models of disease. In this review, we discuss why in vitro models are necessary for translational research and outline the unique advantages of induced pluripotent stem cell (iPSC)-based models over those of current systems. We suggest that iPSC-based models can be patient specific and isogenic lines can be differentiated into many neural cell types for detailed comparisons. iPSC-derived cells can be combined to form small organoids, or large panels of lines can be developed that enable new forms of analysis. iPSC and embryonic stem cell-derived cells can be readily engineered to develop reporters for lineage studies or mechanism of action experiments further extending the utility of iPSC-based systems. We conclude by describing novel technologies that include strategies for the development of diversity panels, novel genomic engineering tools, new three-dimensional organoid systems, and modified high-content screens that may bring toxicology into the 21st century. The strategic integration of these technologies with the advantages of iPSC-derived cell technology, we believe, will be a paradigm shift for toxicology and drug discovery efforts.Disease Modeling D iseases of the central nervous system (CNS) affect a large number of people, but therapeutic intervention is hampered by the lack of useful models for many of these diseases. Current research on human subjects, particularly for drug discovery for CNS diseases, is severely (and appropriately) limited by ethical guidelines. Therefore, surrogate models are needed that share important anatomical, physiological, and genetic features to advance new treatments and therapies for CNS diseases [1].Developing rapid and effective therapies for CNS diseases requires the availability of in vitro models that accurately recapitulate disease phenotypes and predict patient treatment response. A proper model must be both sensitive and predictive while reflecting both normal and disease processes. Equally important, these models should enable the investigation of genetic and environmental risk factors contributing to diseases in a rapid and economical way. Currently used models often do not reflect a typical human response [2-4], despite efforts underway to better characterize these models and increase their preclinical value in predicting safety and efficacy in the clinic [5,6]. Therefore, there is a great need to develop disease-and patient-specific models from cells directly affected in CNS disorders. These cellbased models, we envision, could either replace or supplement current animal models and enable the efficient translation of basic research into the clinical setting. Limitations with current CNS modelsCurrently, drug discovery relies on the use of animalbased or cell-based models, ...

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“…Data from two published methods included embryos treated with chorion intact [10,11] or with chorion removed [12,13].…”

Section: Zebrafish Studiesmentioning

confidence: 99%

“…In addition, zebrafish models are a rapid in vivo method for assessing developmental effects [10][11][12][13]. The goal of this brief communication is to examine if ToxCast and zebrafish results were predictive of targets and activities relevant to in vivo ES and FP endpoints.…”

Section: Introductionmentioning

confidence: 99%

Comparative Toxicity of Endosulfan and Fipronil Insecticides: Utilizing In Vivo and In Vitro Data

Silva¹,

Koshlukova²

2015

J Med Toxicol Clin Forens Med

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Zebrafish developmental screening of the ToxCast™ Phase I chemical library

Cited by 289 publications

References 75 publications

Identification of a Novel Indoline Derivative for in Vivo Fluorescent Imaging of Blood-Brain Barrier Disruption in Animal Models

Identification of a Novel Indoline Derivative for in Vivo Fluorescent Imaging of Blood-Brain Barrier Disruption in Animal Models

Induced Pluripotent Stem Cell Models to Enable In Vitro Models for Screening in the Central Nervous System

Comparative Toxicity of Endosulfan and Fipronil Insecticides: Utilizing In Vivo and In Vitro Data

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