Morphological score assignment guidelines for the dechorionated zebrafish teratogenicity assay

Panzica-Kelly, Julieta M.; Zhang, Cindy X.; Danberry, Tracy L.; Flood, Annette; DeLan, Judiann W.; Brannen, Kimberly C.; Augustine-Rauch, Karen

doi:10.1002/bdrb.20260

Cited by 123 publications

(61 citation statements)

References 3 publications

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“…These features of zebrafish make it possible to maintain them in culture plates, evaluate the teratogenicity in short term, conduct morphological assessment and predict the teratogenicity without any autopsy operation. In -with a simpler experimental protocol and endpoint than in these previously reported ones (Selderslaghs et al, 2009;Brannen et al, 2010;Panzica-Kelly et al, 2010;Selderslaghs et al, 2012). In addition, our method showed in vivo mammalian studies, and 2 teratogens (VPA and methotrexate) were correctly judged as "positive" in this study, however, these were judged as "negative" in the other evaluation methods (Brannen et al, 2010;Selderslaghs et al, 2012).…”

Section: Discussionmentioning

confidence: 46%

“…Other advantages of the tolerant to concentrations of dimethylsulphoxide (DMSO) (Kais et al, 2013) that are generally used as a solvent at drug screening. In addition, a number of laboratories have -opmental toxicology, and have reported their zebrafish developmental toxicity assays demonstrated high conusefulness as a screening tool (Selderslaghs et al, 2009;Brannen et al, 2010;Panzica-Kelly et al, 2010;Selderslaghs et al, 2012). Moreover, a recent study revealed that one of the possible mechanisms of phocet al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Improvement of the evaluation method for teratogenicity using zebrafish embryos

et al. 2014

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ABSTRACTcially for evaluation of the teratogenicity, due to their small size, rapid development, transparency, and maintain them in culture plates, evaluate the teratogenicity in short term, conduct morphological assessment of each organ without any autopsy operation. The purpose of the present study was to improve an evaluation method for the teratogenicity of test compounds with high throughput ability and prediction -were exposed to test compounds from 5-6 to 144 hr post-fertilization, (hpf) corresponding to the organogenesis period. Morphological changes or functional abnormalities induced by test compound treatments were assessed and scored at 11 endpoints, and the potential of teratogenicity was judged based on the score. As a validation assay of the system, the potentials of 59 known teratogenic or non-teratogenic test -rectly predicted in 90% (53/59) of all compounds with low false negative and false positive rates. These valuable tool for early stage screening in drug discovery.

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Section: Discussionmentioning

confidence: 46%

Section: Introductionmentioning

confidence: 99%

Improvement of the evaluation method for teratogenicity using zebrafish embryos

et al. 2014

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“…Swim bladder x xxx blinded observers and was done according to the procedures described earlier [22].…”

Section: Liver -Xxxmentioning

confidence: 99%

Organic Nanovesicular Cargoes for Sustained Drug Delivery: Synthesis, Vesicle Formation, Controlling “Pearling” States, and Terfenadine Loading/Release Studies

Botcha

Dulla

Reddy

et al. 2014

Journal of Nanotechnology

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"Sustained drug delivery systems" which are designed to accomplish long-lasting therapeutic effect are one of the challenging topics in the area of nanomedicine. We developed an innovative strategy to prepare nontoxic and polymer stabilized organic nanovesicles (diameter: 200 nm) from a novel bolaamphiphile, where two hydrogen bonding acetyl cytosine molecules connected to 4,4 -positions of the 2,6-bispyrazolylpyridine through two flexible octyne chains. The nanovesicles behave like biological membrane by spontaneously self-assembling into "pearl-like" chains and subsequently forming long nanotubes (diameter: 150 nm), which further develop into various types of network-junctions through self-organization. For drug loading and delivery applications, the nanovesicles were externally protected with biocompatible poly(ethyleneglycol)-2000 to prevent them from fusion and ensuing tube formation. Nontoxic nature of the nanovesicles was demonstrated by zebrafish teratogenicity assay. Biocompatible nanovesicles were loaded with "terfenadine" drug and successfully utilized to transport and release drug in sustained manner (up to 72 h) in zebrafish larvae, which is recognized as an emerging in vivo model system.

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“…Recently two alternative in vivo model systems, Caenorhabditis elegans (nematode) and Danio rerio (zebrafish) which were well known and used in the field of Developmental and Molecular Biology became noticed as potential promising test systems for hazard assessment (Avila et al, 2012;Ballatori, 2002;Boyd et al, 2016Boyd et al, , 2010Brannen et al, 2010;Hermsen et al, 2011;Leung et al, 2008;Panzica-Kelly et al, 2010;Dhawan et al, 1999;Selderslaghs et al, 2009Selderslaghs et al, , 2012. Both species share high genetic homology to man (~60% for nematodes and 70% for zebrafish), show cell biologically conserved molecular responses (like organ development, cell and tissue signaling etc.)…”

Section: Introductionmentioning

confidence: 99%

Application of Caenorhabditis elegans (nematode) and Danio rerio embryo (zebrafish) as model systems to screen for developmental and reproductive toxicity of Piperazine compounds

Rácz

Wildwater

Rooseboom

et al. 2017

Toxicology in Vitro

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A B S T R A C TTo enable selection of novel chemicals for new processes, there is a recognized need for alternative toxicity screening assays to assess potential risks to man and the environment. For human health hazard assessment these screening assays need to be translational to humans, have high throughput capability, and from an animal welfare perspective be harmonized with the principles of the 3Rs (Reduction, Refinement, Replacement).In the area of toxicology a number of cell culture systems are available but while these have some predictive value, they are not ideally suited for the prediction of developmental and reproductive toxicology (DART). This is because they often lack biotransformation capacity, multicellular or multi-organ complexity, for example, the hypothalamus pituitary gonad (HPG) axis and the complete life cycle of whole organisms.To try to overcome some of these limitations in this study, we have used Caenorhabditis elegans (nematode) and Danio rerio embryos (zebrafish) as alternative assays for DART hazard assessment of some candidate chemicals being considered for a new commercial application. Nematodes exposed to Piperazine and one of the analogs tested showed a slight delay in development compared to untreated animals but only at high concentrations and with Piperazine as the most sensitive compound. Total brood size of the nematodes was also reduced primarily by Piperazine and one of the analogs. In zebrafish Piperazine and analogs showed developmental delays. Malformations and mortality in individual fish were also scored. Significant malformations were most sensitively identified with Piperazine, significant mortality was only observed in Piperazine and only at the higest dose. Thus, Piperazine seemed the most toxic compound for both nematodes and zebrafish.The results of the nematode and zebrafish studies were in alignment with data obtained from conventional mammalian toxicity studies indicating that these have potential as developmental toxicity screening systems. The results of these studies also provided reassurance that none of the Piperazines tested are likely to have any significant developmental and/or reproductive toxicity issues to humans when used in their commercial applications.

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Morphological score assignment guidelines for the dechorionated zebrafish teratogenicity assay

Abstract: To this end, the morphological score system provides information of tissue-specific teratogenicity that has been found to have good concordance with structures found affected in vivo and can also be used to rank compounds based on the severity of malformations.

Cited by 123 publications

References 3 publications

Improvement of the evaluation method for teratogenicity using zebrafish embryos

Improvement of the evaluation method for teratogenicity using zebrafish embryos

Organic Nanovesicular Cargoes for Sustained Drug Delivery: Synthesis, Vesicle Formation, Controlling “Pearling” States, and Terfenadine Loading/Release Studies

Application of Caenorhabditis elegans (nematode) and Danio rerio embryo (zebrafish) as model systems to screen for developmental and reproductive toxicity of Piperazine compounds

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