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Zebrafish as a Model for Assessing Chemical Toxicity

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A special issue of Toxics (ISSN 2305-6304).

Deadline for manuscript submissions: closed (30 June 2016) | Viewed by 37423

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Special Issue Editor

Prof. Dr. Robyn L. Tanguay

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Guest Editor

Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331-4003, USA
Interests: zebrafish; developmental toxicology; systems toxicology; neurotoxicology; nanotoxicology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The zebrafish model (Danio rerio) is now well-accepted for research in genetics, developmental biology, and drug discovery. The exponential rise in the use of the zebrafish model for biomedical related research is largely because of the experimental advantages intrinsic with this system. Advantages include a genome with high homology to the human genome, rapid external embryonic development, tractable genetics, and low overall husbandry costs. Over the past decade many additional advances in toxicology research have elevated zebrafish to a prominent in vivo vertebrate toxicological model. The development of powerful transgenic strains and diverse high data content phenotypic and neurobehavioral screening strategies offer tremendous promise to achieve the goals for toxicology for the 21st century which is to better protect human health by better predicting chemical toxicity. The use of early life stage and adult zebrafish to identify hazardous chemicals and to discover the underlying mechanism that produce adverse responses has increased the acceptance of zebrafish data. In this Special Issue we invite authors to submit manuscripts that further advance the field of toxicology using the zebrafish model. Manuscript focused on the development of new assays, endpoints, toxicity mechanisms, or instrumentation are of particular interest.

Prof. Dr. Robert Tanguay
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

zebrafish
toxicology
chemical screening
behavior
genetics
transgenic

Published Papers (6 papers)

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Research

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2218 KiB

Open AccessArticle

Fish Reproduction Is Disrupted upon Lifelong Exposure to Environmental PAHs Fractions Revealing Different Modes of Action

by Caroline Vignet, Thibaut Larcher, Blandine Davail, Lucette Joassard, Karyn Le Menach, Tiphaine Guionnet, Laura Lyphout, Mireille Ledevin, Manon Goubeau, Hélène Budzinski, Marie-Laure Bégout and Xavier Cousin

Toxics 2016, 4(4), 26; https://doi.org/10.3390/toxics4040026 - 28 Oct 2016

Cited by 21 | Viewed by 5440

Abstract

Polycyclic aromatic hydrocarbons (PAHs) constitute a large family of organic pollutants emitted in the environment as complex mixtures, the compositions of which depend on origin. Among a wide range of physiological defects, PAHs are suspected to be involved in disruption of reproduction. In an aquatic environment, the trophic route is an important source of chronic exposure to PAHs. Here, we performed trophic exposure of zebrafish to three fractions of different origin, one pyrolytic and two petrogenic. Produced diets contained PAHs at environmental concentrations. Reproductive traits were analyzed at individual, tissue and molecular levels. Reproductive success and cumulative eggs number were disrupted after exposure to all three fractions, albeit to various extents depending on the fraction and concentrations. Histological analyses revealed ovary maturation defects after exposure to all three fractions as well as degeneration after exposure to a pyrolytic fraction. In testis, hypoplasia was observed after exposure to petrogenic fractions. Genes expression analysis in gonads has allowed us to establish common pathways such as endocrine disruption or differentiation/maturation defects. Taken altogether, these results indicate that PAHs can indeed disrupt fish reproduction and that different fractions trigger different pathways resulting in different effects. Full article

(This article belongs to the Special Issue Zebrafish as a Model for Assessing Chemical Toxicity)

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1554 KiB

Open AccessArticle

Effects of Estrogen, Nitric Oxide, and Dopamine on Behavioral Locomotor Activities in the Embryonic Zebrafish: A Pharmacological Study

by Vania Murcia, Luke Johnson, Meredith Baldasare, Bridgette Pouliot, John McKelvey, Brandon Barbery, Julie Lozier, Wade E. Bell and James E. Turner

Toxics 2016, 4(4), 24; https://doi.org/10.3390/toxics4040024 - 26 Sep 2016

Cited by 2 | Viewed by 4274

Abstract

Nitric oxide (NO) has been shown to affect motor function. Specifically, NO has been shown to act through regulation of dopamine (DA) release, transporter function, and the elicitation of neuroprotection/neurodegeneration of neurons. Recently, zebrafish have been proposed to be a new model for the study of various types of motor dysfunctions, since neurotoxin damage to their nigrostriatal-like neurons exhibit motor anomalies similar to those of mammalian models and human patients. Results from this study demonstrate that when NO synthesis is inhibited in zebrafish, using a neuronal NO synthase inhibitor (nNOSI), a condition called ‘listless’ occurs, where the fish lack swimming abilities, are rigid, and have difficulty maintaining balance. Additionally, co-treatment with either NO or estrogen (E2), an upstream regulator of NO synthase, can rescue fish from the ‘listless’ phenotype caused by exposure to the neurotoxin 6-hydroxydopamine (6 OHDA). In turn, NO deprived zebrafish were rescued from the ‘listless’ phenotype when co-treated with L-DOPA, a precursor to DA. Interestingly, the longer fish are exposed to a 6 OHDA + nNOSI co-treatment, the slower the recovery after washout, compared to a single treatment of each. Most significantly, NO involvement in the motor homeostasis of the embryonic zebrafish was shown to be expressed through the NO-cGMP-dependent pathway, and response to nNOSI treatments is developmentally regulated. In conclusion, these results indicate that there is a link between E2, NO, and DA systems that regulate motor functions in the embryonic zebrafish. Full article

(This article belongs to the Special Issue Zebrafish as a Model for Assessing Chemical Toxicity)

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1369 KiB

Open AccessArticle

Differences in Reproductive Behavior between Spawning and Non-Spawning Zebrafish Pairs and the Effects of 17α-Ethinylestradiol (EE2)

by Per G. Henriksen, Kristian Beedholm and Erik Baatrup

Toxics 2016, 4(3), 22; https://doi.org/10.3390/toxics4030022 - 06 Sep 2016

Cited by 5 | Viewed by 4931

Abstract

Reproductive success manifested by spawning and fertilization, in most fish, depends partly on an appropriate courtship behavior by both sexes. The zebrafish reproductive behavior can be resolved in some of its constituent elements by a computerized vision system and described in unbiased quantitative terms. Pairs of adult male and female zebrafish were monitored with automatic video tracking at 16 Hz for 45 min in a tank with a spawning area in one corner. Subsequently, spawning, if any, was registered and the swimming behavior and mutual interactions of the two fish were quantified. Further, temporal and frequency distributions of average velocity and turning rate were produced. It is demonstrated that the courtship behavior in spawning pairs differs markedly from non-spawning pairs with differences in both male and female behavior. EE2 (17α-ethinylestradiol), a contraceptive hormone found in aquatic environments, has only a slight effect on these behavior differences between spawning and non-spawning pairs. Full article

(This article belongs to the Special Issue Zebrafish as a Model for Assessing Chemical Toxicity)

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2558 KiB

Open AccessArticle

Evaluation of Common Use Brominated Flame Retardant (BFR) Toxicity Using a Zebrafish Embryo Model

by Crystal Y. Usenko, Erika L. Abel, Aaron Hopkins, Gerardo Martinez, Jonathan Tijerina, Molly Kudela, Nick Norris, Lana Joudeh and Erica D. Bruce

Toxics 2016, 4(3), 21; https://doi.org/10.3390/toxics4030021 - 02 Sep 2016

Cited by 39 | Viewed by 6755

Abstract

Brominated flame retardants (BFRs) are used to reduce the flammability of plastics, textiles, and electronics. BFRs vary in their chemical properties and structures, and it is expected that these differences alter their biological interactions and toxicity. Zebrafish were used as the model organism for assessing the toxicity of nine structurally-diverse BFRs. In addition to monitoring for overt toxicity, the rate of spontaneous movement, and acetylcholinesterase and glutathione-S-transferase (GST) activities were assessed following exposure. The toxicities of BFRs tested can be ranked by LC50 as tetrabromobisphenol A (TBBPA) < 4,4′-isopropylidenebis[2-(2,6-dibromophenoxyl)ethanol] (TBBPA-OHEE) < Pentabromochlorocyclohexane (PBCH) < 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB) < hexabromocyclododecane (HBCD) < hexabromobenzene (HBB) < Tetrabromophthalic anhydride (PHT4). No adverse effect was observed in di(2-ethylhexyl) tetrabromophthalate (TBPH) or dibromoneopentyl glycol (DBNPG)-treated embryos. The rate of spontaneous movement was decreased in a concentration-dependent manner following exposure to four of the nine compounds. GST activity was elevated following treatment with PBCH, TBBPA, HBCD, and HBB. The results indicate that exposure to several BFRs may activate an antioxidant response and alter behavior during early development. Some of the BFRs, such as TBBPA and TBBPA-OHEE, induced adverse effects at concentrations lower than chemicals that are currently banned. These results suggest that zebrafish are sensitive to exposure to BFRs and can be used as a comparative screening model, as well as to determine alterations in behavior following exposure and probe mechanisms of action. Full article

(This article belongs to the Special Issue Zebrafish as a Model for Assessing Chemical Toxicity)

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3062 KiB

Open AccessArticle

Assessment of Toxicological Perturbations and Variants of Pancreatic Islet Development in the Zebrafish Model

by Karilyn E. Sant, Haydee M. Jacobs, Jiali Xu, Katrina A. Borofski, Larry G. Moss, Jennifer B. Moss and Alicia R. Timme-Laragy

Toxics 2016, 4(3), 20; https://doi.org/10.3390/toxics4030020 - 02 Sep 2016

Cited by 18 | Viewed by 6759

Abstract

The pancreatic islets, largely comprised of insulin-producing beta cells, play a critical role in endocrine signaling and glucose homeostasis. Because they have low levels of antioxidant defenses and a high perfusion rate, the endocrine islets may be a highly susceptible target tissue of chemical exposures. However, this endpoint, as well as the integrity of the surrounding exocrine pancreas, is often overlooked in studies of developmental toxicology. Disruption of development by toxicants can alter cell fate and migration, resulting in structural alterations that are difficult to detect in mammalian embryo systems, but that are easily observed in the zebrafish embryo model (Danio rerio). Using endogenously expressed fluorescent protein markers for developing zebrafish beta cells and exocrine pancreas tissue, we documented differences in islet area and incidence rates of islet morphological variants in zebrafish embryos between 48 and 96 h post fertilization (hpf), raised under control conditions commonly used in embryotoxicity assays. We identified critical windows for chemical exposures during which increased incidences of endocrine pancreas abnormalities were observed following exposure to cyclopamine (2–12 hpf), Mono-2-ethylhexyl phthalate (MEHP) (3–48 hpf), and Perfluorooctanesulfonic acid (PFOS) (3–48 hpf). Both islet area and length of the exocrine pancreas were sensitive to oxidative stress from exposure to the oxidant tert-butyl hydroperoxide during a highly proliferative critical window (72 hpf). Finally, pancreatic dysmorphogenesis following developmental exposures is discussed with respect to human disease. Full article

(This article belongs to the Special Issue Zebrafish as a Model for Assessing Chemical Toxicity)

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Review

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878 KiB

Open AccessReview

Zebrafish Get Connected: Investigating Neurotransmission Targets and Alterations in Chemical Toxicity

by Katharine A. Horzmann and Jennifer L. Freeman

Toxics 2016, 4(3), 19; https://doi.org/10.3390/toxics4030019 - 27 Aug 2016

Cited by 106 | Viewed by 8567

Abstract

Neurotransmission is the basis of neuronal communication and is critical for normal brain development, behavior, learning, and memory. Exposure to drugs and chemicals can alter neurotransmission, often through unknown pathways and mechanisms. The zebrafish (Danio rerio) model system is increasingly being used to study the brain and chemical neurotoxicity. In this review, the major neurotransmitter systems, including glutamate, GABA, dopamine, norepinephrine, serotonin, acetylcholine, histamine, and glutamate are surveyed and pathways of synthesis, transport, metabolism, and action are examined. Differences between human and zebrafish neurochemical pathways are highlighted. We also review techniques for evaluating neurological function, including the measurement of neurotransmitter levels, assessment of gene expression through transcriptomic analysis, and the recording of neurobehavior. Finally examples of chemical toxicity studies evaluating alterations in neurotransmitter systems in the zebrafish model are reviewed. Full article

(This article belongs to the Special Issue Zebrafish as a Model for Assessing Chemical Toxicity)

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