Special Issue "Fish Models for Human Toxicology"

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Toxicology".

Deadline for manuscript submissions: 31 August 2022 | Viewed by 6260

Special Issue Editors

Dr. Demetrio Raldúa
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Guest Editor
Department Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18, 08034 Barcelona, Spain
Interests: fish neurotoxicology; zebrafish model; fish developmental neurotoxicology
Special Issues, Collections and Topics in MDPI journals
Dr. Benjamin Piña
E-Mail
Guest Editor
Institute of Environmental Assessment and Water Research, IDAEA-CSIC, Barcelona, Catalunya 08034, Spain
Interests: ecotoxicology; molecular biology; biochemistry; omics
Dr. Natalia Garcia-Reyero
E-Mail
Guest Editor
Environmental Laboratory, US Army Engineer Research & Development Center, Vicksburg, MS 39180, USA
Interests: toxicogenomics; predictive toxicology; zebrafis; adverse outcome pathways

Special Issue Information

Dear Colleagues,

Whereas many of the human toxidromes have already been modelized in rodents, only a few models have been developed and conveniently validated in fish. Before proposing the use of any fish model of human toxidromes, the validity of the developed model should always be tested. Thus, an intensive effort should be made to characterize the effects of the toxicant at different levels of biological organization, from molecular to behavioral, in the developed model as a part of the validation process. As fish are considered a less-sentient organism, even adult fish models of human toxidromes fully meet the 3Rs principles. This advantage makes fish ideal for the initial screening and prioritization of chemicals providing protection against the toxidromes, as only the most promising drugs would be further validated in a rodent model. This approach makes it possible to obtain highly predictive results for humans, because if one drug provides protection against a neurotoxic in both fish and rodents (two phylogenetically distant vertebrate models), it is likely working through highly conserved mechanisms, and there is thus a high probability that it will also be useful in protecting humans against the same toxidrome.

This Special Issue on “Fish Models for Human Toxicology” aims to highlight the research into the development and validation of human toxidromes using well-established fish models in biomedicine, such as zebrafish or medaka. We are also interested in studies using fish models to increase our current mechanistic understanding of human toxidromes, identifying new potential therapeutic targets and developing more effective therapies.

Authors are invited and welcome to submit original research papers, reviews, and short communications.

Dr. Demetrio Raldúa
Dr. Benjamin Piña
Dr. Natalia Garcia-Reyero
Guest Editors

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 1800 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

  • fish models
  • toxicology
  • adverse outcome pathways
  • treatment
  • validity process
  • mechanistic approach

Published Papers (7 papers)

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Research

Article
Evaluating Phenotypic and Transcriptomic Responses Induced by Low-Level VOCs in Zebrafish: Benzene as an Example
Toxics 2022, 10(7), 351; https://doi.org/10.3390/toxics10070351 - 27 Jun 2022
Viewed by 145
Abstract
Urban environments are plagued by complex mixtures of anthropogenic volatile organic compounds (VOCs), such as mixtures of benzene, toluene, ethylene, and xylene (BTEX). Sources of BTEX that drive human exposure include vehicle exhaust, industrial emissions, off-gassing of building material, as well as oil [...] Read more.
Urban environments are plagued by complex mixtures of anthropogenic volatile organic compounds (VOCs), such as mixtures of benzene, toluene, ethylene, and xylene (BTEX). Sources of BTEX that drive human exposure include vehicle exhaust, industrial emissions, off-gassing of building material, as well as oil spillage and leakage. Among the BTEX mixture, benzene is the most volatile compound and has been linked to numerous adverse health outcomes. However, few studies have focused on the effects of low-level benzene on exposure during early development, which is a susceptible window when hematological, immune, metabolic, and detoxification systems are immature. In this study, we used zebrafish to conduct a VOC exposure model and evaluated phenotypic and transcriptomic responses following 0.1 and 1 ppm benzene exposure during the first five days of embryogenesis (n = 740 per treatment). The benzene body burden was 2 mg/kg in 1 ppm-exposed larval zebrafish pools and under the detection limit in 0.1 ppm-exposed fish. No observable phenotypic changes were found in both larvae except for significant skeletal deformities in 0.1 ppm-exposed fish (p = 0.01) compared with unexposed fish. Based on transcriptomic responses, 1 ppm benzene dysregulated genes that were implicated with the development of hematological system, and the regulation of oxidative stress response, fatty acid metabolism, immune system, and inflammatory response, including apob, nfkbiaa, serpinf1, foxa1, cyp2k6, and cyp2n13 from the cytochrome P450 gene family. Key genes including pik3c2b, pltp, and chia.2 were differentially expressed in both 1 and 0.1 ppm exposures. However, fewer transcriptomic changes were induced by 0.1 ppm compared with 1 ppm. Future studies are needed to determine if these transcriptomic responses during embryogenesis have long-term consequences at levels equal to or lower than 1 ppm. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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Article
Developmental, Behavioral and Transcriptomic Changes in Zebrafish Embryos after Smoke Dye Exposure
Toxics 2022, 10(5), 210; https://doi.org/10.3390/toxics10050210 - 22 Apr 2022
Viewed by 590
Abstract
(1) Background: Disperse Blue 14, Disperse Red 9, Solvent Red 169 and Solvent Yellow 33 have been used to color smoke; however, they have not been comprehensively assessed for their potential health hazards. (2) Methods: To assess the effects of these dyes, zebrafish [...] Read more.
(1) Background: Disperse Blue 14, Disperse Red 9, Solvent Red 169 and Solvent Yellow 33 have been used to color smoke; however, they have not been comprehensively assessed for their potential health hazards. (2) Methods: To assess the effects of these dyes, zebrafish embryos were exposed from 6 to 120 h post fertilization (hpf) to 10–55 µM Disperse Red 9, 1–50 µM Solvent Red 169, 7.5–13.5 µM Solvent Yellow 33 or 133–314 µM Disperse Blue 14. Embryos were monitored for adverse effects on gene expression at 48 hpf as well as for mortality, development and behavior at 120 hpf. The dyes were examined for their potential to cross the blood–brain barrier. (3) Results: Solvent Yellow 33 and Disperse Blue 14 impaired development and behavior at all concentrations. Disperse Red 9 impaired behavior at all concentrations and development at all concentrations except for 10 µM. Solvent Red 169 caused no effects. Mortality was only seen in Disperse Blue 14 at 261.5 and 314 µM. Gene expression indicated impacts on neurodevelopment and folate and retinol metabolism as potential mechanisms of toxicity. (4) Conclusions: Smoke dyes have a high potential for causing developmental changes and neurotoxicity and should be examined more closely using comprehensive approaches as used here. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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Article
MPTP-Treated Zebrafish Recapitulate ‘Late-Stage’ Parkinson’s-like Cognitive Decline
Toxics 2022, 10(2), 69; https://doi.org/10.3390/toxics10020069 - 04 Feb 2022
Cited by 1 | Viewed by 1260
Abstract
The zebrafish is a promising model species in biomedical research, including neurotoxicology and neuroactive drug screening. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes degeneration of dopaminergic neurons and is commonly used to model Parkinson’s disease (PD) in laboratory animals, including zebrafish. However, cognitive phenotypes in MPTP-evoked experimental [...] Read more.
The zebrafish is a promising model species in biomedical research, including neurotoxicology and neuroactive drug screening. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes degeneration of dopaminergic neurons and is commonly used to model Parkinson’s disease (PD) in laboratory animals, including zebrafish. However, cognitive phenotypes in MPTP-evoked experimental PD models remain poorly understood. Here, we established an LD50 (292 mg/kg) for intraperitoneal MPTP administration in adult zebrafish, and report impaired spatial working memory (poorer spontaneous alternation in the Y-maze) in a PD model utilizing fish treated with 200 µg of this agent. In addition to conventional behavioral analyses, we also employed artificial intelligence (AI)-based approaches to independently and without bias characterize MPTP effects on zebrafish behavior during the Y-maze test. These analyses yielded a distinct cluster for 200-μg MPTP (vs. other) groups, suggesting that high-dose MPTP produced distinct, computationally detectable patterns of zebrafish swimming. Collectively, these findings support MPTP treatment in adult zebrafish as a late-stage experimental PD model with overt cognitive phenotypes. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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Article
Behavioral Effects of Buspirone in Juvenile Zebrafish of Two Different Genetic Backgrounds
Toxics 2022, 10(1), 22; https://doi.org/10.3390/toxics10010022 - 07 Jan 2022
Cited by 1 | Viewed by 441
Abstract
Anxiety continues to represent a major unmet medical need. Despite the availability of numerous anxiolytic drugs, a large proportion of patients do not respond well to current pharmacotherapy, or their response diminishes with chronic drug application. To discover novel compounds and to investigate [...] Read more.
Anxiety continues to represent a major unmet medical need. Despite the availability of numerous anxiolytic drugs, a large proportion of patients do not respond well to current pharmacotherapy, or their response diminishes with chronic drug application. To discover novel compounds and to investigate the mode of action of anxiolytic drugs, animal models have been proposed. The zebrafish is a novel animal model in this research. It is particularly appropriate, as it has evolutionarily conserved features, and drug administration can be employed in a non-invasive manner by immersing the fish into the drug solution. The first step in the analysis of anxiolytic drugs with zebrafish is to test reference compounds. Here, we investigate the effects of buspirone hydrochloride, an anxiolytic drug often employed in the human clinic. We utilize two genetically distinct populations of zebrafish, ABSK, derived from the quasi-inbred AB strain, and WT, a genetically heterogeneous wild-type population. We placed juvenile (10–13-day, post-fertilization, old) zebrafish singly in petri dishes containing one of four buspirone concentrations (0 mg/L control, 5 mg/L, 20 mg/L or 80 mg/L) for 1 h, with each fish receiving a single exposure to one concentration, a between subject experimental design. Subsequently, we recorded the behavior of the zebrafish for 30 min using video-tracking. Buspirone decreased distance moved, number of immobility episodes and thigmotaxis, and it increased immobility duration and turn angle in a quasi-linear dose dependent but genotype independent manner. Although it is unclear whether these changes represent anxiolysis in zebrafish, the results demonstrate that behavioral analysis of juvenile zebrafish may be a sensitive and simple way to quantify the effects of human anxiolytic drugs. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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Article
Exploring Neurobehaviour in Zebrafish Embryos as a Screening Model for Addictiveness of Substances
Toxics 2021, 9(10), 250; https://doi.org/10.3390/toxics9100250 - 07 Oct 2021
Cited by 1 | Viewed by 835
Abstract
Tobacco use is the leading cause of preventable death worldwide and is highly addictive. Nicotine is the main addictive compound in tobacco, but less is known about other components and additives that may contribute to tobacco addiction. The zebrafish embryo (ZFE) has been [...] Read more.
Tobacco use is the leading cause of preventable death worldwide and is highly addictive. Nicotine is the main addictive compound in tobacco, but less is known about other components and additives that may contribute to tobacco addiction. The zebrafish embryo (ZFE) has been shown to be a good model to study the toxic effects of chemicals on the neurological system and thus may be a promising model to study behavioral markers of nicotine effects, which may be predictive for addictiveness. We aimed to develop a testing protocol to study nicotine tolerance in ZFE using a locomotion test with light-dark transitions as behavioral trigger. Behavioral experiments were conducted using three exposure paradigms: (1) Acute exposure to determine nicotine’s effect and potency. (2) Pre-treatment with nicotine dose range followed by a single dose of nicotine, to determine which pre-treatment dose is sufficient to affect the potency of acute nicotine. (3) Pre-treatment with a single dose combined with acute exposure to a dose range to confirm the hypothesized decreased potency of the acute nicotine exposure. These exposure paradigms showed that (1) acute nicotine exposure decreased ZFE activity in response to dark conditions in a dose-dependent fashion; (2) pre-treatment with increasing concentrations dose-dependently reversed the effect of acute nicotine exposure; and (3) a fixed pre-treatment dose of nicotine induced a decreased potency of the acute nicotine exposure. This effect supported the induction of tolerance to nicotine by the pre-treatment, likely through neuroadaptation. The interpretation of these effects, particularly in view of prediction of dependence and addictiveness, and suitability of the ZFE model to test for such effects of other compounds than nicotine, are discussed. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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Article
Differential Modulation of the Central and Peripheral Monoaminergic Neurochemicals by Deprenyl in Zebrafish Larvae
Toxics 2021, 9(6), 116; https://doi.org/10.3390/toxics9060116 - 23 May 2021
Cited by 2 | Viewed by 929
Abstract
Zebrafish embryos and larvae are vertebrate models increasingly used in translational neuroscience research. Behavioral impairment induced by the exposure to neuroactive or neurotoxic compounds is commonly linked to changes in modulatory neurotransmitters in the brain. Although different analytical methods for determining monoaminergic neurochemicals [...] Read more.
Zebrafish embryos and larvae are vertebrate models increasingly used in translational neuroscience research. Behavioral impairment induced by the exposure to neuroactive or neurotoxic compounds is commonly linked to changes in modulatory neurotransmitters in the brain. Although different analytical methods for determining monoaminergic neurochemicals in zebrafish larvae have been developed, these methods have been used only on whole larvae, as the dissection of the brain of hundreds of larvae is not feasible. This raises a key question: Are the changes in the monoaminergic profile of the whole larvae predictive of the changes in the brain? In this study, the levels of ten monoaminergic neurotransmitters were determined in the head, trunk, and the whole body of zebrafish larvae in a control group and in those treated for 24 h with 5 M deprenyl, a prototypic monoamine-oxidase B inhibitor, eight days post-fertilization. In control larvae, most of the monoaminergic neurochemicals were found at higher levels in the head than in the trunk. Significant changes were found in the distribution of some neurochemicals after deprenyl-treatment, with serotonin and norepinephrine increasing in both the head and the trunk, whereas dopamine, L-DOPA, and homovanillic acid levels were only modulated in the head. In fact, the highly significant increase in dopamine levels observed in the head after deprenyl-treatment was not detected in the whole-body analysis. These results indicate that the analysis of neurotransmitters in the zebrafish larvae whole-body should not be used as a general surrogate of the brain. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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Article
Zebrafish Embryonic Exposure to BPAP and Its Relatively Weak Thyroid Hormone-Disrupting Effects
Toxics 2020, 8(4), 103; https://doi.org/10.3390/toxics8040103 - 13 Nov 2020
Cited by 2 | Viewed by 1113
Abstract
Safe endocrine-disrupting alternatives for bisphenol A (BPA) are needed because its adverse health effects have become a public concern. Some bisphenol analogues (bisphenol F and S) have been applied, but their endocrine-disrupting potential is either not negligible or weaker than that of BPA. [...] Read more.
Safe endocrine-disrupting alternatives for bisphenol A (BPA) are needed because its adverse health effects have become a public concern. Some bisphenol analogues (bisphenol F and S) have been applied, but their endocrine-disrupting potential is either not negligible or weaker than that of BPA. However, the endocrine-disrupting potential of bisphenol AP (BPAP), another BPA alternative, has not yet been fully assessed. Hence, we evaluated the thyroid hormone (TH)-disrupting potency of BPAP because THs are essential endocrine hormones. Zebrafish embryos were exposed to BPAP (0, 18.2, 43.4, or 105.9 μg/L) for 120 h, and TH levels, the transcription of 16 TH-related genes, the transcriptome, development, and behavior were evaluated. In our study, a decrease in T4 level was observed only at the maximum nonlethal concentration, but significant changes in the T3 and TSHβ levels were not detected. BPAP did not cause significant changes in transcription and gene ontology enrichment related to the TH system. Developmental and behavioral changes were not observed. Despite T4 level reduction, other markers were not significantly affected by BPAP. These might indicate that BPAP has weak or negligible potency regarding TH disruption as a BPA alternative. This study might provide novel information on the TH-disrupting potential of BPAP. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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