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The same CYP activity assays were performed in adult zebrafish liver microsomes (ZLM) to serve as
a reference for the embryos. The difference in photon energy between the two lasers corresponds
with the 2845 cm ?1 stretch vibration of CH 2 groups. These embryos display rich visual-behaviors
that can be used to screen drugs for treating retinal degeneration (RD). Subscribe to receive issue
release notifications and newsletters from MDPI journals. In graph ( a, b ), developmental stages
with values below the LLOQ were excluded from statistical analysis. Early life stage exposure to
environmental chemicals may play a role in obesity by altering adipogenesis; however, robust in vivo
methods to quantify these effects are lacking. All rights are reserved, including those for text and
data mining, AI training, and similar technologies. Persistent organic pollutants (POPs) are
widespread in the environment and some may be neurotoxic. Resources Dive into our extensive
resources on the topic that interests you. The zebrafish has emerged as an invaluable model to
examine substance toxicity on vertebrate development, particularly on cardiac development. All
manuscripts are thoroughly refereed through a single-blind peer-review process. Analysis was
performed after three days of treatment (immersion) or three days after treatment (injection), at 6
dpf. Over the next several days, olfactory organ morphology, epithelial structure, and anti-calretinin
labeling returned to control-like conditions, although the ability to perceive bile salts remained lost
until day 14. The ZFET results showed that even materials with low bacterial contamination showed
high toxicity or high teratogenicity, probably because of the presence of unknown chemical additives.
Numbers linked to each dot correspond to a methylxanthine compound, as reported in Table 2. A
sizeable portion of the societal drain from cocaine abuse results from the complications of in utero
drug exposure. Photon hormesis refers to the phenomenon where the biological effect of ionizing
radiation with a high linear energy transfer (LET) value is diminished by photons with a low LET
value. Here, we report the development of an integrative evaluation method for down and feather
materials to assess bacterial contamination and in vivo toxicity. The lines joining the data points are
drawn to guide the eye only. Confirming Transformation of Fluorescent-Labeled Tumor Cells by Cell
Transplantation into Irradiated Recipient Animals VI. Conclusions: We established an integrative
evaluation method for down and feather safety, based on bacterial contamination with in vivo
toxicity testing. The parallels in organ development and common bodily functions make them a
reliable stand-in for experiments looking into how new treatments could affect future human
patients. These materials tend to become more allergenic as they become contaminated with
microorganisms, in addition to being subjected to several kinds of chemical treatments. There are
recorded instances of nocturnal behavior leading to false positives in other animal models that could
have been avoided by using Zebrafish. Zebrafish offer a number of advantages as a model in
longitudinal toxicology studies and are quite sensitive physiologically and behaviorally to cocaine.
The color bar between 0 and 5 dpf, i.e., between 0 and 120 h post-fertilization, indicates the period
of zebrafish organogenesis. Open Access is an initiative that aims to make scientific research freely
available to all. Our results demonstrate the need for preliminary testing to assess potential feed
component-related effects on the overall nutritional balance. Numbers linked to each dot correspond
to a methylxanthine compound, as reported in Table 2. Comparison Between Teleosts and Other
Vertebrates IV.
The yellow frame indicates the region of interest in the embryo or larva. Here, we will review the
advantages of using the zebrafish model for drug discovery and toxicological and phenotypical
screening. Morpholino-mediated knockdown of intraflagellar transport protein Ift17 2 in
Tg(wt1b:EGFP) embryos was used to induce large glomerular cysts representing a robustly scorable
phenotypic readout. Persistent organic pollutants (POPs) are widespread in the environment and
some may be neurotoxic. The image shows a maximum projection of the GFP channel overlaid with
the bright-field channel. Pigment cells were again confined to the lamina propria (arrowheads).
Scanning electron microscopy revealed the apical surface of the sensory region was absent of ciliated
structures, but microvilli were still present. Small fish are an excellent experimental model to screen
endocrine-disrupting compounds, but current fish-based assays to detect endocrine disruption have
not been standardized yet, meaning that there is not consensus on endpoints and biomarkers to be
measured. Abbreviations: hpf indicates hours post fertilization, dpf represents days post fertilization.
The present paper studied the X-ray-induced targeted effect in irradiated zebrafish embryos ( Danio
rerio ), as well as a non-targeted effect in bystander naive embryos partnered with irradiated
embryos, and examined the influence of exogenous nitric oxide (NO) on these targeted and non-
targeted effects. Editor’s Choice articles are based on recommendations by the scientific editors of
MDPI journals from around the world. The present study evaluated in detail the developmental
effects seen in zebrafish embryos exposed to triadimefon, confirmed and expanded upon previous
phenotypic findings. We also review other existing models of neurodevelopmental disorders, and the
current efforts in developing and testing compounds with potential therapeutic value. Bacterial
composition of each sample is depicted in Figures S2 and S3. ( c ) Quantification of contaminated
bacterial in unwashed and washed samples. Environmental contamination by trinitrotoluene is of
global concern due to its widespread use in military ordnance and commercial explosives. They
produce a large number of small and rapidly-developing embryos. An odorant is administered in one
tube while water is simultaneously delivered in the other tube. Finally, tools to study epigenetic
modifications in zebrafish, including changes in genome-wide DNA methylation, histone
modifications and miRNA expression, are also described in this review. Sharpton Institute of
Molecular Biology, University of Oregon, Eugene, OR, USA Karen Guillemin Humans and the
Microbiome Program, CIFAR, Toronto, Ontario, Canada Karen Guillemin Authors Keaton Stagaman
View author publications You can also search for this author in. Overall, this study further
demonstrates the sensitivity of embryo bioassays as a high-throughput approach for testing the
toxicity of emerging pollutants. Paclobutrazol (PBZ) is a widely used fungicide that shows toxicity
to aquatic embryos, probably through rain-wash. Introduction II. The PMR Behavior III. Methods IV.
Discussion Chapter 23: Designing Zebrafish Chemical Screens I. ZeGlobalTox is an innovative assay
that sequentially integrates in vivo cardio-, neuro-, and hepatotoxicity assessment in the same animal,
thus impacting strongly in the 3Rs principles. Small fish are an excellent experimental model to
screen endocrine-disrupting compounds, but current fish-based assays to detect endocrine disruption
have not been standardized yet, meaning that there is not consensus on endpoints and biomarkers to
be measured. ISPRS International Journal of Geo-Information (IJGI). In ( A, C ) separate controls
(“control D” and “control K”), with pH and conductivity adjusted to those of the field water
samples, were included. Olfaction mediates behaviors pivotal for survival, such as feeding, mating,
social behavior, and danger assessment. Various drugs and substances, such as ketamine and nicotine,
are tested on zebrafish to determine effects which might occur in humans. Protein phosphatase 2A
activity was expressed as nmol of free PO 4 ?3 released per min using increasing amounts of total
protein (?g). Drugs in development include treatment for infectious diseases, cardiovascular diseases,
neurological disorders, cancers and several rare diseases.
Despite known long-term persistence in groundwater and soil, the toxicological profile of
trinitrotoluene and other explosive wastes have not been systematically measured using in vivo
biological assays. X -axis: APAP concentration; Y -axis: response; CdCl 2 concentration groups are
statistically significantly separated and shown as black—0 ?M; red—1 ?M; green—3.2 ?M; dark
blue—10 ?M; light blue—32 ?M CdCl 2 at embryonic exposure. This study showed that zebrafish
individuals with well-controlled infection display not only an efficient Th1 immune response but
also an adequate Th2 response. The zebrafish, however, offers considerably more as a model species
and is now used in many different research fields including basic developmental biology,
neurobiology, and immunology. Zebrafish share most major organs with humans, making them
highly translatable for many types of research. Moreover, thanks to a well-conserved physiology, the
pharmacological behavior and metabolism of several drugs have been screened in zebrafish with
effects similar to humans. Larvae were exposed to A6 between 1 and 5 dpf ( left panel ) and
between 1 and 6 dpf ( right panel ), and reinnervation was examined 1, 2 and 3 days after the cut; (
B ) Extent of hair cell regeneration expressed as number of hair cells present 1 day after complete
ablation of all hair cells through copper sulfate treatment at 7 dpf. Journal of Otorhinolaryngology,
Hearing and Balance Medicine (JOHBM). The study contributes novel data regarding the
metabolism of BPS and BP2 in a fish model and shows that phase II conjugation pathways are
already functional in 4-dpf-old zebrafish. In animals, hatching represents the transition point from a
developing embryo to a free-living individual, the larva. Teams Enable groups of users to work
together to streamline your digital publishing. Eisen, Susan F. Farmer, Karen J. Guillemin, Michael L.
Resources Dive into our extensive resources on the topic that interests you. International Journal of
Environmental Research and Public Health (IJERPH). Zebrafish vhl Mutants Develop Pronephros
Abnormalities XI. Embryos and larvae develop normally under anesthesia with tricaine methane
sulfonate (MS222), which makes them ideal for non-invasive time lapse imaging. Overall, this study
further demonstrates the sensitivity of embryo bioassays as a high-throughput approach for testing
the toxicity of emerging pollutants. One of the most toxic variants of this family is microcystin-LR
(MCLR) which is a potent inhibitor of protein phosphatase 2A (PP2A) and induces cytoskeleton
alterations. The neurotoxicity of methylmercury (MeHg) is well characterised, and the ameliorating
effects of selenium have been described. In order to be human-readable, please install an RSS reader.
Scores above the cut-off (1,3) are displayed by a color gradient. Using in vitro models, we recently
showed that OH-PBDEs disrupt oxidative phosphorylation (OXPHOS), an essential process in
energy metabolism. Comparisons are separately made for the five data points within case (i) or case
(ii) through ANOVA. When p ? 0.05 from ANOVA, post-hoc t -tests are further performed to assess
the difference between tested A Y or AX Y groups and the corresponding A C or AX C group.
Images were captured using a florescent microscope with 40. Both swimming trajectory and time
spent in each quadrant can be assessed with this test. Adobe Express Go from Adobe Express
creation to Issuu publication. Epigenetic alterations are a possible underlying mechanism. The
zebrafish is being increasingly used in biomedical research and drug discovery to conduct large-scale
compound screening. Advances in genetic and epigenetic research of the zebrafish, including gene
knockout and transgenesis technologies, allow for better understanding of molecular mechanisms of
toxic action. Developmental stages of the organogenesis period are represented as h post-fertilization
(hpf).
RDH5 converts 11- cis -retinol to 11- cis -retinal. These materials tend to become more allergenic as
they become contaminated with microorganisms, in addition to being subjected to several kinds of
chemical treatments. Mercury (Hg) is a global pollutant that may exert its toxic effects on living
organisms and is found in both aquatic and terrestrial ecosystems in three chemical forms; elemental,
organic, and inorganic. Biotransformation processes are well-recognized as a critical factor
influencing toxic response, but major gaps of knowledge exist. Finally, tools to study epigenetic
modifications in zebrafish, including changes in genome-wide DNA methylation, histone
modifications and miRNA expression, are also described in this review. All submissions that pass
pre-check are peer-reviewed. Full genome microarray analyses of RNA isolated from eye tissue
revealed that the number of affected transcripts was substantially higher in PTU- than in TBBPA-
treated larvae. Using in vitro models, we recently showed that OH-PBDEs disrupt oxidative
phosphorylation (OXPHOS), an essential process in energy metabolism. FET test showed a different
pattern of toxicity with different methylxanthines. The horizontal dotted line represents the lower
limit of quantification (LLOQ). In Europe, the toxicological safety of genetically modified (GM)
crops is routinely evaluated using rodent feeding trials, originally designed for testing oral toxicity of
chemical compounds. Control fish made significantly more turns after exposure to either mixture. (
A ) At 2 days following zinc sulfate treatment, fish did not show a statistically significant response
to amino acids; however, there appeared to be a subset of fish that showed some response to the
odor (2 days) and others who exhibited no change in behavior in response to the odor (2 days’).
European Journal of Investigation in Health, Psychology and Education (EJIHPE). Contributions on
high throughput screening, monitoring and safety assessment of chemicals are invited, as well as
new insights on the effects in chemical exposure in zebrafish models of human diseases. Zebrafish-
based platforms have recently emerged as a useful tool for toxicity testing as they combine the
advantages of in vitro and in vivo methodologies. There is an Article Processing Charge (APC) for
publication in this. Relative condition factor and length were evaluated every 4 weeks, reproduction
parameters and quality of the offspring were analyzed at the start of the experiment and at week 12.
Regarding the lack of publications, the histology analysis was performed after exposure to E2 to find
effective treatment on bone mineralization of developing zebrafish larvae. High Content Screening
with zebrafish embryos and larvae in toxicity and safety assays have been highly successful in this
regard. Fish from all embryonic treatment groups not treated with cocaine as adults were combined
into a single group for comparative purposes (Unt CPP). The zebrafish ( Danio rerio ) embryo is
currently explored as an alternative for developmental toxicity testing. Journal of Experimental and
Theoretical Analyses (JETA). We show here that all OH-PBDEs tested, both individually and as
mixtures, resulted in a concentration-dependant delay in development in zebrafish embryos.
Zebrafish exploitation in high-throughput drug screening is becoming an important tool to assess the
toxicity and efficacy of novel drugs. Recent studies show that predispositions for NCDs may arise
from early-life exposure to low concentrations of environmental contaminants. Using in vitro
models, we recently showed that OH-PBDEs disrupt oxidative phosphorylation (OXPHOS), an
essential process in energy metabolism. Phenotype-based high-rate screenings of skincare products
(nanotoxicity) are one such area where zebrafish have shown potential. The neurotoxicity of
methylmercury (MeHg) is well characterised, and the ameliorating effects of selenium have been
described. In this study, we have used zebrafish to model the effects of embryonic pre-exposure to
cocaine on development and on subsequent cardiovascular physiology and cocaine-induced
conditioned place preference (CPP) in longitudinal adults. Zebrafish embryo is emerging as an
important tool for behavior analysis as well as toxicity testing.
Among other advantages, these models are 3R-compliant and are fit for screening purposes.
Moreover, we will report the latest compounds and small molecules under investigation in melanoma
zebrafish models. Finally, our results illustrate that the use of commercial control diets (CCDs) and
null segregant (NS) controls (helpful for assessing potential effects of the transformation process)
would be valuable additions to GM safety assessment strategies. Despite being a non-mammalian
animal, the zebrafish. Articles Get discovered by sharing your best content as bite-sized articles.
Olfaction mediates behaviors pivotal for survival, such as feeding, mating, social behavior, and
danger assessment. We aimed to develop and optimize methods for advancing the use of zebrafish
feeding trials for the. In this way, DNA methylation may be affected at a critical developmental
stage, causing the observed apical phenotypes. Resources Dive into our extensive resources on the
topic that interests you. Among other advantages, these models are 3R-compliant and are fit for
screening purposes. Despite known long-term persistence in groundwater and soil, the toxicological
profile of trinitrotoluene and other explosive wastes have not been systematically measured using in
vivo biological assays. Non-communicable diseases (NCDs) are a major cause of premature
mortality. Images of 48 hpf old embryos exposed to different concentrations ( upper row).
Environmental contamination by trinitrotoluene is of global concern due to its widespread use in
military ordnance and commercial explosives. Of note, the sensitivity of this assay system is high
enough to detect a distinct compound at a concentration that does not cause morphological effects.
Images of 48 hpf old embryos exposed to different concentrations ( upper row). The results for
parathion show an improved predictivity of the toxic potential of the compound. The histogram
shows data from one of three experiments measuring heart rate in zebrafish larvae exposed to
different doses of cocaine for three days and then allowed one day of recovery before testing.
Conclusions Chapter 16: Zebrafish Models of Rhabdomyosarcoma I. Results indicate that the POP
mixture increases the swimming speed of larval zebrafish following exposure between 48 to 96 hpf.
Very little structure remained and it was not possible to distinguish sensory and non-sensory
epithelia. Cocaine pre-exposure during development results in a bell-shaped response curve for CPP
in longitudinal adults. Each group contains at least 20 embryos; Scale bar: 50 ?m. The animal is
placed in a new arena containing refuge areas (represented by a black box) or risk areas (shallow
area), and the swimming pattern is analyzed. These treated larvae also showed a dose dependent
response in heart rate that persisted 24 h after drug cessation. The green and purple highlighted
regions represent the 95% and 99% confidence intervals, respectively, of each critical point
(minimum or maximum) of mRNA expression. Finally, the drop in the apoptotic counts at 24 hpf due
to photon hormesis was explained by bringing the apoptotic events earlier to 20 hpf, which strongly
supported the removal of aberrant cells through apoptosis as an underlying mechanism for photon
hormesis. Methodology for Zebrafish Studies of Basement Membrane Composition and Function IV.
The yellow frame indicates the region of interest in the embryo or larva. WT for a selection of
endpoints: length, hepatosomatic index, liver carbohydrate and protein contents, gonadosomatic
index.
The source of the chemoattractants also remains to be established. Articles Get discovered by
sharing your best content as bite-sized articles. The demonstrated toolset covers all the aspects of a
complex whole organism screening assay and can be adapted to other organs, specimens or
applications. In that line, cardio-, neuro-, and hepatotoxicities are among the main reasons behind
the retirement of drugs in clinical phases and post market withdrawal. Finally, it might allow the
Replacement of classical species, such as rodents and larger mammals, thanks to its high predictivity
(Specificity: 89%, Sensitivity: 68% and Accuracy: 78%). International Journal of Turbomachinery,
Propulsion and Power (IJTPP). Our findings show that the POP mixture and PFOS can have a
similar effect on behaviour, yet alter the expression of genes relevant to neurological development
differently. Instructor? Request an Exam Copy As an IntechOpen contributor, you can buy this book
for an Exclusive Author price with discounts from 30% to 50% on retail price. Ball, Jelena Periz-
Stanacev, Waleed F. A. Marei, Anna Tochwin, Isabelle J. Social Posts Create on-brand social posts
and Articles in minutes. Journal of Otorhinolaryngology, Hearing and Balance Medicine (JOHBM).
Larvae were exposed to A6 between 1 and 5 dpf ( left panel ) and between 1 and 6 dpf ( right panel
), and reinnervation was examined 1, 2 and 3 days after the cut; ( B ) Extent of hair cell regeneration
expressed as number of hair cells present 1 day after complete ablation of all hair cells through
copper sulfate treatment at 7 dpf. The zebrafish genome shows up to 80% similarity with human
disease-associated genes. The numbered boxes represent the steps that were conducted in this study.
Nevertheless, the capacity to metabolically convert xenobiotics by zebrafish eleuthero embryos is
supposedly low. Results of first and second assays are normalized to the respective control assay, for
both endpoints. The lines joining the data points are drawn to guide the eye only. All submissions
that pass pre-check are peer-reviewed. It Refines the drug toxicity evaluation through novel
physiological parameters. Zebrafish are a popular vertebrate model in drug discovery. The zebrafish (
Danio rerio ) embryo is currently explored as an alternative for developmental toxicity testing. For
many of us, mice and monkeys come to mind when thinking about animal models. Zinc sulfate
appears to have a greater effect on ciliated olfactory sensory neurons than on microvillous olfactory
sensory neurons, suggesting differential effects on sensory neuron subtypes. The other parameters
show possible adaptions to the analysis or output, i.e., data transformation, selection, removal, and
scaling. Paclobutrazol (PBZ) is a widely used fungicide that shows toxicity to aquatic embryos,
probably through rain-wash. Around 3 days into its larval stage, zebrafish develop anatomical
structures. Maintaining the Barrier Function of Blood Vessels III. This method is also suitable for
testing of other organ-related toxicities subject to the organs and tissues expressing fluorescent
proteins in transgenic zebrafish lines. Zebrafish Tools and Protocols Chapter 6: Zebrafish as a Model
for Hemorrhagic Stroke I. Using 3 H-labeled chemicals, we examined the fate of two estrogenic
emerging contaminants, benzophenone-2 (BP2) and bisphenol S (BPS), in 4-day embryos and adult
zebrafish.