Toxics

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17 pages, 2114 KiB

Open AccessArticle

Wild Zebrafish Sentinels: Biological Monitoring of Site Differences Using Behavior and Morphology

by Jeffrey R. Kelly, Sierra G. Shelton, Danita K. Daniel, Anuradha Bhat, Rubina Mondal, Fahren Nipple, Halima Amro, Myra E. Bower, Gabriel Isaac, Gillian McHaney, Emilia P. Martins and Delia S. Shelton

Toxics 2021, 9(7), 165; https://doi.org/10.3390/toxics9070165 - 12 Jul 2021

Cited by 7 | Viewed by 4162

Abstract

Environmental change poses a devastating risk to human and environmental health. Rapid assessment of water conditions is necessary for monitoring, evaluating, and addressing this global health danger. Sentinels or biological monitors can be deployed in the field using minimal resources to detect water [...] Read more.

Environmental change poses a devastating risk to human and environmental health. Rapid assessment of water conditions is necessary for monitoring, evaluating, and addressing this global health danger. Sentinels or biological monitors can be deployed in the field using minimal resources to detect water quality changes in real time, quickly and cheaply. Zebrafish (Danio rerio) are ideal sentinels for detecting environmental changes due to their biomedical tool kit, widespread geographic distribution, and well-characterized phenotypic responses to environmental disturbances. Here, we demonstrate the utility of zebrafish sentinels by characterizing phenotypic differences in wild zebrafish between two field sites in India. Site 1 was a rural environment with flowing water, low-hypoxic conditions, minimal human-made debris, and high iron and lead concentrations. Site 2 was an urban environment with still water, hypoxic conditions, plastic pollution, and high arsenic, iron, and chromium concentrations. We found that zebrafish from Site 2 were smaller, more cohesive, and less active than Site 1 fish. We also found sexually dimorphic body shapes within the Site 2, but not the Site 1, population. Advancing zebrafish sentinel research and development will enable rapid detection, evaluation, and response to emerging global health threats. Full article

(This article belongs to the Special Issue Advanced Zebrafish Model for Environmental Health Sciences Research)

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11 pages, 924 KiB

Open AccessArticle

In Vivo Effects of Neonicotinoid-Sulfoximine Insecticide Sulfoxaflor on Acetylcholinesterase Activity in the Tissues of Zebrafish (Danio rerio)

by Petek Piner Benli and Mehmet Çelik

Toxics 2021, 9(4), 73; https://doi.org/10.3390/toxics9040073 - 1 Apr 2021

Cited by 12 | Viewed by 3225

Abstract

Sulfoxaflor is the first member of the neonicotinoid-sulfoximine insecticides that acts as an agonist of nicotinic acetylcholine receptors (nAChRs). This study investigated the acute effects of sulfoxaflor on acetylcholinesterase (AChE; EC 3.1.1.7) enzyme activity in the brain and muscle tissues of zebrafish ( [...] Read more.

Sulfoxaflor is the first member of the neonicotinoid-sulfoximine insecticides that acts as an agonist of nicotinic acetylcholine receptors (nAChRs). This study investigated the acute effects of sulfoxaflor on acetylcholinesterase (AChE; EC 3.1.1.7) enzyme activity in the brain and muscle tissues of zebrafish (Danio rerio) as a model organism. The zebrafish were exposed to 0.87 mg/L (2.5% of 96 h 50% lethal concentration (LC₅₀), 1.75 mg/L (5% of 96 h LC₅₀) and 3.51 mg/L (10% of 96 h LC₅₀) of sulfoxaflor for 24 h–48 h and 96 h periods. AChE enzyme activities were analysed by a spectrophotometric method in the brain and muscle tissues. The results of this study showed that in vivo acute sulfoxaflor exposure significantly increased AChE enzyme activity in the brain and muscle tissues of zebrafish. The induction percentages of AChE were between 10 and 83%, and 19 and 79% for brain and muscle tissues, respectively. As a result, it was found that sulfoxaflor had an effect on AChE enzyme activity in the two main tissues containing this enzyme, and it can be considered as a potential neuroactive compound for zebrafish. Full article

(This article belongs to the Special Issue Advanced Zebrafish Model for Environmental Health Sciences Research)

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11 pages, 2120 KiB

Open AccessFeature PaperArticle

Developmental Hazard of Environmentally Persistent Free Radicals and Protective Effect of TEMPOL in Zebrafish Model

by Xia Guan, Lisa Truong, Slawomir M. Lomnicki, Robyn L. Tanguay and Stephania A. Cormier

Toxics 2021, 9(1), 12; https://doi.org/10.3390/toxics9010012 - 16 Jan 2021

Cited by 6 | Viewed by 2862

Abstract

Environmentally persistent free radicals (EPFRs) can be detected in ambient PM_2.5, cigarette smoke, and soils and are formed through combustion and thermal processing of organic materials. The hazards of EPFRs are largely unknown. In this study, we assess the developmental toxicity [...] Read more.

Environmentally persistent free radicals (EPFRs) can be detected in ambient PM_2.5, cigarette smoke, and soils and are formed through combustion and thermal processing of organic materials. The hazards of EPFRs are largely unknown. In this study, we assess the developmental toxicity of EPFRs and the ability of TEMPOL (4-Hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl) to protect against such hazards using zebrafish embryos. Particles containing EPFRs were acquired by dosing dichlorobenzene (DCB) vapor on the Cab-o-sil/5% CuO particles at 230 °C in vacuo (referred to as DCB-230). The particles were suspended in ultrapure water to make 1 mg/mL of stock solution from which series dilution was undertaken to obtain 10, 20, 30, 40, 50, 60, 80, and 100 µg/mL final test solutions, which were then placed in individual wells with a 4 h postfertilization (hpf) zebrafish embryo. Plates were run in duplicate to obtain a sample size of 24 animals per concentration; 12 embryos were exposed per concentration per plate. Statistical analysis of the morphology endpoints was performed. We investigated overt toxicity responses to DCB-230 in a 22-endpoint battery that included developing zebrafish from 24–120 hpf. Exposure to concentrations greater than 60 µg/mL of DCB-230 induced high mortality in the developmental zebrafish model. Exposure to EPFRs induced developmental hazards that were closely related to the concentrations of free radicals and EPFRs. The potential protective effects of TEMPOL against EPFRs’ toxicity in zebrafish were investigated. Exposure to EPFRs plus TEMPOL shifted the concentration to an induced 50% adverse effect (EC50), from 23.6 to 30.8 µg/mL, which verifies TEMPOL’s protective effect against EPFRs in the early phase of zebrafish development. Full article

(This article belongs to the Special Issue Advanced Zebrafish Model for Environmental Health Sciences Research)

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15 pages, 1291 KiB

Open AccessArticle

Phylogenetic Integration Reveals the Zebrafish Core Microbiome and Its Sensitivity to Environmental Exposures

by Thomas J. Sharpton, Keaton Stagaman, Michael J. Sieler, Jr., Holly K. Arnold and Edward W. Davis II

Toxics 2021, 9(1), 10; https://doi.org/10.3390/toxics9010010 - 15 Jan 2021

Cited by 22 | Viewed by 4731

Abstract

Zebrafish are increasingly used to study how environmental exposures impact vertebrate gut microbes. However, we understand little about which microbial taxa are common to the zebrafish gut across studies and facilities. Here, we define the zebrafish core gut microbiome to resolve microbiota that [...] Read more.

Zebrafish are increasingly used to study how environmental exposures impact vertebrate gut microbes. However, we understand little about which microbial taxa are common to the zebrafish gut across studies and facilities. Here, we define the zebrafish core gut microbiome to resolve microbiota that are both relatively robust to study or facility effects and likely to drive proper microbiome assembly and functioning due to their conservation. To do so, we integrated publicly available gut microbiome 16S gene sequence data from eight studies into a phylogeny and identified monophyletic clades of gut bacteria that are unexpectedly prevalent across individuals. Doing so revealed 585 core clades of bacteria in the zebrafish gut, including clades within Aeromonas, Pseudomonas, Cetobacterium, Shewanella, Chitinibacter, Fluviicola, Flectobacillus, and Paucibacter. We then applied linear regression to discern which of these core clades are sensitive to an array of different environmental exposures. We found that 200 core clades were insensitive to any exposure we assessed, while 134 core clades were sensitive to more than two exposures. Overall, our analysis defines the zebrafish core gut microbiome and its sensitivity to exposure, which helps future studies to assess the robustness of their results and prioritize taxa for empirical assessments of how gut microbiota mediate the effects of exposure on the zebrafish host. Full article

(This article belongs to the Special Issue Advanced Zebrafish Model for Environmental Health Sciences Research)

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10 pages, 1152 KiB

Open AccessFeature PaperArticle

Morphological and Behavioral Effects in Zebrafish Embryos after Exposure to Smoke Dyes

by Kimberly T. To, Lindsey St. Mary, Allyson H. Wooley, Mitchell S. Wilbanks, Anthony J. Bednar, Edward J. Perkins, Lisa Truong, Robyn L. Tanguay and Natàlia Garcia-Reyero

Toxics 2021, 9(1), 9; https://doi.org/10.3390/toxics9010009 - 10 Jan 2021

Cited by 10 | Viewed by 3185

Abstract

Solvent Violet 47 (SV47) and Disperse Blue 14 (DB14) are two anthraquinone dyes that were previously used in different formulations for the production of violet-colored smoke. Both dyes have shown potential for toxicity; however, there is no comprehensive understanding of their effects. Zebrafish [...] Read more.

Solvent Violet 47 (SV47) and Disperse Blue 14 (DB14) are two anthraquinone dyes that were previously used in different formulations for the production of violet-colored smoke. Both dyes have shown potential for toxicity; however, there is no comprehensive understanding of their effects. Zebrafish embryos were exposed to SV47 or DB14 from 6 to 120 h post fertilization (hpf) to assess the dyes’ potential adverse effects on developing embryos. The potential ability of both dyes to cross the blood–brain barrier was also assessed. At concentrations between 0.55 and 5.23 mg/L, SV47 showed a dose-dependent increase in mortality, jaw malformation, axis curvature, and edemas. At concentrations between 0.15 and 7.54 mg/L, DB14 did not have this same dose-dependence but had similar morphological outcomes at the highest doses. Nevertheless, while SV47 showed significant mortality from 4.20 mg/L, there was no significant mortality on embryos exposed to DB14. Regardless, decreased locomotor movement was observed at all concentrations of DB14, suggesting an adverse neurodevelopmental effect. Overall, our results showed that at similar concentrations, SV47 and DB14 caused different types of phenotypic effects in zebrafish embryos. Full article

(This article belongs to the Special Issue Advanced Zebrafish Model for Environmental Health Sciences Research)

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11 pages, 3465 KiB

Open AccessFeature PaperArticle

Comparative Analysis of Neurotoxicity of Six Phthalates in Zebrafish Embryos

by Cong Minh Tran, Trinh Ngoc Do and Ki-Tae Kim

Toxics 2021, 9(1), 5; https://doi.org/10.3390/toxics9010005 - 7 Jan 2021

Cited by 39 | Viewed by 5447

Abstract

The effects and underlying mechanisms of phthalates on neurotoxicity remain unclear as compared with the potentials of these substances as endocrine disruptors. The locomotor activities of zebrafish embryos were investigated upon exposure to six phthalates: dimethyl phthalate (DMP), diethyl phthalate (DEP), benzyl butyl [...] Read more.

The effects and underlying mechanisms of phthalates on neurotoxicity remain unclear as compared with the potentials of these substances as endocrine disruptors. The locomotor activities of zebrafish embryos were investigated upon exposure to six phthalates: dimethyl phthalate (DMP), diethyl phthalate (DEP), benzyl butyl phthalate (BBzP), di-2-ethylhexyl phthalate (DEHP), di-n-octyl phthalate (DnOP), and diisononyl phthalate (DiNP). Moreover, changes in fluorescence intensity in the green fluorescent protein (GFP) transgenic (Tg) lines Tg(HuC:eGFP), Tg(sox10:eGFP), and Tg(mbp:GFP) were measured after exposure to six phthalates, and changes in the expression profiles of genes involved in the cholinergic (ache) and dopaminergic systems (dat, th, and drd1b) were assessed. Exposure to BBzP, DEHP, and DiNP affected larval behaviors, whereas exposure to DMP, DEP, and DnOP revealed no alterations. A reduced expression of Tg(HuC:eGFP) was observed upon exposure to BBzP, DEHP, and DiNP. The expression of Tg(sox10:eGFP) and Tg(mbp:GFP) was reduced only in response to BBzP and DiNP, respectively. Further, exposure to DiNP upregulated ache and drd1b. The upregulation of ache and downregulation of drd1b was observed in DEHP-exposed groups. Exposure to BBzP suppressed th expression. These observations indicate that exposure to phthalates impaired embryogenesis of the neurological system and neurochemicals in zebrafish embryos, although the detailed mechanisms varied among the individual phthalates. Further mechanistic studies are needed to better understand the causality between phthalate exposure and neurotoxicity. Full article

(This article belongs to the Special Issue Advanced Zebrafish Model for Environmental Health Sciences Research)

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13 pages, 1861 KiB

Open AccessArticle

Comparison of the Zebrafish Embryo Toxicity Assay and the General and Behavioral Embryo Toxicity Assay as New Approach Methods for Chemical Screening

by John C. Achenbach, Cindy Leggiadro, Sandra A. Sperker, Cindy Woodland and Lee D. Ellis

Toxics 2020, 8(4), 126; https://doi.org/10.3390/toxics8040126 - 21 Dec 2020

Cited by 24 | Viewed by 3930

Abstract

The movement away from mammalian testing of potential toxicants and new chemical entities has primarily led to cell line testing and protein-based assays. However, these assays may not yet be sufficient to properly characterize the toxic potential of a chemical. The zebrafish embryo [...] Read more.

The movement away from mammalian testing of potential toxicants and new chemical entities has primarily led to cell line testing and protein-based assays. However, these assays may not yet be sufficient to properly characterize the toxic potential of a chemical. The zebrafish embryo model is widely recognized as a potential new approach method for chemical testing that may provide a bridge between cell and protein-based assays and mammalian testing. The Zebrafish Embryo Toxicity (ZET) model is increasingly recognized as a valuable toxicity testing platform. The ZET assay focuses on the early stages of embryo development and is considered a more humane model compared to adult zebrafish testing. A complementary model has been developed that exposes larvae to toxicants at a later time point during development where body patterning has already been established. Here we compare the toxicity profiles of 20 compounds for this General and Behavioral Toxicity (GBT) assay to the ZET assay. The results show partially overlapping toxicity profiles along with unique information provided by each assay. It appears from this work that these two assays applied together can strengthen the use of zebrafish embryos/larvae as standard toxicity testing models. Full article

(This article belongs to the Special Issue Advanced Zebrafish Model for Environmental Health Sciences Research)

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14 pages, 5867 KiB

Open AccessArticle

An Embryonic Zebrafish Model to Screen Disruption of Gut-Vascular Barrier upon Exposure to Ambient Ultrafine Particles

by Kyung In Baek, Yi Qian, Chih-Chiang Chang, Ryan O’Donnell, Ehsan Soleimanian, Constantinos Sioutas, Rongsong Li and Tzung K. Hsiai

Toxics 2020, 8(4), 107; https://doi.org/10.3390/toxics8040107 - 19 Nov 2020

Cited by 2 | Viewed by 3425

Abstract

Epidemiological studies have linked exposure to ambient particulate matter (PM) with gastrointestinal (GI) diseases. Ambient ultrafine particles (UFP) are the redox-active sub-fraction of PM2.5, harboring elemental and polycyclic aromatic hydrocarbons from urban environmental sources including diesel and gasoline exhausts. The gut-vascular barrier (GVB) [...] Read more.

Epidemiological studies have linked exposure to ambient particulate matter (PM) with gastrointestinal (GI) diseases. Ambient ultrafine particles (UFP) are the redox-active sub-fraction of PM2.5, harboring elemental and polycyclic aromatic hydrocarbons from urban environmental sources including diesel and gasoline exhausts. The gut-vascular barrier (GVB) regulates paracellular trafficking and systemic dissemination of ingested microbes and toxins. Here, we posit that acute UFP ingestion disrupts the integrity of the intestinal barrier by modulating intestinal Notch activation. Using zebrafish embryos, we performed micro-gavage with the fluorescein isothiocynate (FITC)-conjugated dextran (FD10, 10 kDa) to assess the disruption of GVB integrity upon UFP exposure. Following micro-gavage, FD10 retained in the embryonic GI system, migrated through the cloaca. Conversely, co-gavaging UFP increased transmigration of FD10 across the intestinal barrier, and FD10 fluorescence occurred in the venous capillary plexus. Ingestion of UFP further impaired the mid-intestine morphology. We performed micro-angiogram of FD10 to corroborate acute UFP-mediated disruption of GVB. Transient genetic and pharmacologic manipulations of global Notch activity suggested Notch regulation of the GVB. Overall, our integration of a genetically tractable embryonic zebrafish and micro-gavage technique provided epigenetic insights underlying ambient UFP ingestion disrupts the GVB. Full article

(This article belongs to the Special Issue Advanced Zebrafish Model for Environmental Health Sciences Research)

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Graphical abstract

11 pages, 1621 KiB

Open AccessArticle

Development of a Larval Zebrafish Model for Acute Organophosphorus Nerve Agent and Pesticide Exposure and Therapeutic Evaluation

by Jeffrey A. Koenig, Cindy Acon Chen and Tsung-Ming Shih

Toxics 2020, 8(4), 106; https://doi.org/10.3390/toxics8040106 - 17 Nov 2020

Cited by 6 | Viewed by 2484

Abstract

Organophosphorus compound exposure remains a present threat through agricultural accidents, warfare, or terrorist activity. The primary mechanism of organophosphorus toxicity is through inhibition of the enzyme acetylcholinesterase, with current emergency treatment including anticholinergics, benzodiazepines, and oxime reactivators. However, a need for more effective [...] Read more.

Organophosphorus compound exposure remains a present threat through agricultural accidents, warfare, or terrorist activity. The primary mechanism of organophosphorus toxicity is through inhibition of the enzyme acetylcholinesterase, with current emergency treatment including anticholinergics, benzodiazepines, and oxime reactivators. However, a need for more effective and broadly acting countermeasures remains. This study aimed to develop larval zebrafish as a high-throughput model for evaluating novel therapeutics against acute organophosphorus exposure. Larval zebrafish at six days post-fertilization were exposed to acute concentrations of seven organophosphorus compounds and treated with one of three oximes. Lethality studies indicated similar relative toxicity to that seen in the established rodent model, with chemical warfare agents proving more lethal than organophosphorus pesticides. Additionally, the organophosphorus-specific response for oxime reactivation of acetylcholinesterase was comparable to what has been previously reported. Behavioral studies measuring the visual motor response demonstrated greater efficacy for centrally acting oxime compounds than for those that are contained to the peripheral tissue. Overall, these results support the use of this larval zebrafish model as a high-throughput screening platform for evaluating novel treatments following acute organophosphorus exposure. Full article

(This article belongs to the Special Issue Advanced Zebrafish Model for Environmental Health Sciences Research)

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15 pages, 1889 KiB

Open AccessArticle

Systematic Assessment of Exposure Variations on Observed Bioactivity in Zebrafish Chemical Screening

by Lindsay B. Wilson, Lisa Truong, Michael T. Simonich and Robyn L. Tanguay

Toxics 2020, 8(4), 87; https://doi.org/10.3390/toxics8040087 - 14 Oct 2020

Cited by 13 | Viewed by 2998

Abstract

The embryonic zebrafish is a powerful tool for high-throughput screening of chemicals. While this model has significant potential for use in safety assessments and chemical prioritization, a lack of exposure protocol harmonized across laboratories has limited full model adoption. To assess the potential [...] Read more.

The embryonic zebrafish is a powerful tool for high-throughput screening of chemicals. While this model has significant potential for use in safety assessments and chemical prioritization, a lack of exposure protocol harmonized across laboratories has limited full model adoption. To assess the potential that exposure protocols alter chemical bioactivity, we screened a set of eight chemicals and one 2D nanomaterial across four different regimens: (1) the current Tanguay laboratory’s standard protocol of dechorionated embryos and static exposure in darkness; (2) exposure with chorion intact; (3) exposure under a 14 h light: 10 h dark cycle; and (4) exposure with daily chemical renewal. The latter three regimens altered the concentrations, resulting in bioactivity of the test agents compared to that observed with the Tanguay laboratory’s standard regimen, though not directionally the same for each chemical. The results of this study indicate that with the exception for the 2D nanomaterial, the screening design did not change the conclusion regarding chemical bioactivity, just the nominal concentrations producing the observed activity. Since the goal of tier one chemical screening often is to differentiate active from non-active chemicals, researchers could consider the trade-offs regarding cost, labor, and sensitivity in their study design without altering hit rates. Taken further, these results suggest that it is reasonably feasible to reach agreement on a standardized exposure regiment, which will promote data sharing without sacrificing data content. Full article

(This article belongs to the Special Issue Advanced Zebrafish Model for Environmental Health Sciences Research)

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Review

Jump to: Research

19 pages, 1177 KiB

Open AccessFeature PaperReview

Uncovering Evidence for Endocrine-Disrupting Chemicals That Elicit Differential Susceptibility through Gene-Environment Interactions

by Dylan J. Wallis, Lisa Truong, Jane La Du, Robyn L. Tanguay and David M. Reif

Toxics 2021, 9(4), 77; https://doi.org/10.3390/toxics9040077 - 6 Apr 2021

Cited by 4 | Viewed by 3462

Abstract

Exposure to endocrine-disrupting chemicals (EDCs) is linked to myriad disorders, characterized by the disruption of the complex endocrine signaling pathways that govern development, physiology, and even behavior across the entire body. The mechanisms of endocrine disruption involve a complex system of pathways that [...] Read more.

Exposure to endocrine-disrupting chemicals (EDCs) is linked to myriad disorders, characterized by the disruption of the complex endocrine signaling pathways that govern development, physiology, and even behavior across the entire body. The mechanisms of endocrine disruption involve a complex system of pathways that communicate across the body to stimulate specific receptors that bind DNA and regulate the expression of a suite of genes. These mechanisms, including gene regulation, DNA binding, and protein binding, can be tied to differences in individual susceptibility across a genetically diverse population. In this review, we posit that EDCs causing such differential responses may be identified by looking for a signal of population variability after exposure. We begin by summarizing how the biology of EDCs has implications for genetically diverse populations. We then describe how gene-environment interactions (GxE) across the complex pathways of endocrine signaling could lead to differences in susceptibility. We survey examples in the literature of individual susceptibility differences to EDCs, pointing to a need for research in this area, especially regarding the exceedingly complex thyroid pathway. Following a discussion of experimental designs to better identify and study GxE across EDCs, we present a case study of a high-throughput screening signal of putative GxE within known endocrine disruptors. We conclude with a call for further, deeper analysis of the EDCs, particularly the thyroid disruptors, to identify if these chemicals participate in GxE leading to differences in susceptibility. Full article

(This article belongs to the Special Issue Advanced Zebrafish Model for Environmental Health Sciences Research)

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