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Toxics
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Zebrafish as a Model for Pharmacological and Toxicological Research
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Zebrafish as a Model for Pharmacological and Toxicological Research

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

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 11783

Special Issue Editor

Dr. Pavla Lakdawala

E-Mail Website
Guest Editor
Department of Animal Protection and Welfare & Veterinary Public Health, University of Veterinary Sciences Brno, Palackeho tr. 1, Brno, Czech Republic
Interests: ecotoxicology; aquatic ecosystems; fish; food safety; pharmaceuticals; pesticides
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

For decades, zebrafish has been a prefered model organism used in various research fields, such as toxicology, developmental biology, medicine, and many others. Zebrafish popularity is mainly based on small body size, easy husbandry, rapid development, and optical  translucency of early life stages. Moreover, the development of zebrafish is well-described and the genome fully sequenced. Thanks to that, zebrafish can be used to investigate the mechanism of action of various substances, evaluate ecotoxicity, and environmental toxicants (including pharmaceutical residues in surface waters), and can be used in new drug development.

In this Special Issue, we welcome any novel studies with a focus on using zebrafish as a model for pharmacological and toxicological research.

Dr. Pavla Lakdawala
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
  • pharmaceutical residues
  • model organis
  • aquatic ecotoxicology

Published Papers (5 papers)

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Research

16 pages, 5570 KiB  
Article
Discovering Novel Bioactivities of Controversial Food Additives by Means of Simple Zebrafish Embryotoxicity (ZET) Assays
by Dinh Duy-Thanh, Nguyen Bich-Ngoc, François Van den Bossche, Nguyen Lai-Thanh and Marc Muller
Toxics 2023, 11(1), 8; https://doi.org/10.3390/toxics11010008 - 22 Dec 2022
Viewed by 2163
Abstract
The rising concerns about controversial food additives’ potential hazardous properties require extensive yet animal-minimized testing strategies. Zebrafish embryos are the ideal in vivo model representing both human and environmental health. In this study, we exposed zebrafish embryos to eight controversial food additives. Our [...] Read more.
The rising concerns about controversial food additives’ potential hazardous properties require extensive yet animal-minimized testing strategies. Zebrafish embryos are the ideal in vivo model representing both human and environmental health. In this study, we exposed zebrafish embryos to eight controversial food additives. Our results indicate that Sodium Benzoate is a Cat.3 aquatic toxicant, while Quinoline Yellow is a strong teratogen. At high concentrations, non-toxic chemicals induced similar phenotypes, suggesting the impact of ionic strength and the applicability of the darkened yolk phenotype as an indicator of nephrotoxicity. Three food additives showed unpredicted bioactivities on the zebrafish embryos: Brilliant Blue could weaken the embryonic yolk, Quinoline Yellow may interfere with nutrient metabolism, and Azorubine induced precocious zebrafish hatching. In conclusion, the zebrafish embryo is ideal for high throughput chemical safety and toxicity screening, allowing systematic detection of biological effects—especially those unexpected by targeted in vitro and in silico models. Additionally, our data suggest the need to reconsider the safety status of food additives Quinoline Yellow, Brilliant Blue, Sodium Benzoate, and other controversial food additives in further studies, as well as pave the way to further applications based on the newly found properties of Brilliant Blue and Azorubine. Full article
(This article belongs to the Special Issue Zebrafish as a Model for Pharmacological and Toxicological Research)
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11 pages, 1775 KiB  
Article
Atrazine Exposure Induces Hepatic Metabolism Disorder in Male Adult Zebrafish
by Hu Zhang, Xiaofang Wang, Mingrong Qian and Yuanxiang Jin
Toxics 2022, 10(7), 400; https://doi.org/10.3390/toxics10070400 - 19 Jul 2022
Cited by 4 | Viewed by 1914
Abstract
Atrazine (ATZ) is a herbicide used in agricultural production and has been detected in surface water due to its widespread use worldwide. This may pose a threat to the health of aquatic animals. To explore the ATZ−induced hepatic metabolism disorder, male zebrafish were [...] Read more.
Atrazine (ATZ) is a herbicide used in agricultural production and has been detected in surface water due to its widespread use worldwide. This may pose a threat to the health of aquatic animals. To explore the ATZ−induced hepatic metabolism disorder, male zebrafish were exposed to 300 and 1000 μg/L ATZ for 21 days, respectively. The results revealed that ATZ exposure significantly reduced hepatic triglyceride (TG) levels, while significantly (p < 0.05) increased pyruvate (PYR) and total cholesterol (TC) levels. In addition, the liver sample from the 1000 μg/L ATZ−treated group was used for GC/MS metabolomic analysis. The principal component analysis (PCA) model showed significant separation of the 1000 μg/L ATZ group from the control group, indicating that ATZ exposure altered hepatic metabolism in male adult zebrafish. A total of 29 significantly (p < 0.05) different metabolites were observed and identified in the ATZ−treated group. Moreover, the most disturbed pathways by ATZ were the arginine and proline metabolic pathways, followed by the glutathione metabolic pathway. Three and two metabolites were significantly altered in the arginine and proline metabolic pathways and glutathione metabolic pathway, respectively. Based on these results, we suggested that ATZ was capable of altering liver metabolism in zebrafish and that its ecological risk to aquatic organisms cannot be ignored. Full article
(This article belongs to the Special Issue Zebrafish as a Model for Pharmacological and Toxicological Research)
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12 pages, 2775 KiB  
Article
Environmental Impact of Pharmaceutical Pollutants: Synergistic Toxicity of Ivermectin and Cypermethrin
by Davide Di Paola, Carmelo Iaria, Fabio Marino, Enrico Gugliandolo, Cristian Piras, Rosalia Crupi, Salvatore Cuzzocrea, Nunziacarla Spanò, Domenico Britti and Alessio Filippo Peritore
Toxics 2022, 10(7), 388; https://doi.org/10.3390/toxics10070388 - 12 Jul 2022
Cited by 3 | Viewed by 2574
Abstract
Veterinary antiparasitic pharmaceuticals as well as pesticides have been detected in surface waters, and they may cause several toxic effects in this environmental compartment. In the present study, we evaluated the toxicity after exposure of different concentration of ivermectin (IVM; 50, 100, and [...] Read more.
Veterinary antiparasitic pharmaceuticals as well as pesticides have been detected in surface waters, and they may cause several toxic effects in this environmental compartment. In the present study, we evaluated the toxicity after exposure of different concentration of ivermectin (IVM; 50, 100, and 200 μg L−1) and cypermethrin (CYP; 5, 10, and 25 μg L−1) and the combination of these two compounds at non-toxic concentration (IVM 100 + CYP 5 μg L−1) in zebrafish embryos. Combination of IVM at 100 μg L−1 with CYP at 5 μg L−1 exposure induced hatching delay and malformations at 96 hpf in zebrafish larvae as well as significant induction of cell death in zebrafish larvae. At the same time, the two single concentrations of IVM and CYP did not show a toxic effect on zebrafish development. In conclusion, our study suggests that IVM and CYP show a synergistic effect at common, ineffective concentrations, promoting malformation and cell death in fish development. Full article
(This article belongs to the Special Issue Zebrafish as a Model for Pharmacological and Toxicological Research)
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12 pages, 1697 KiB  
Article
Developmental Toxic Effects of Thiram on Developing Zebrafish (Danio rerio) Embryos
by Bala Murali Krishna Vasamsetti, Kyongmi Chon, Juyeong Kim, Jin-A Oh, Chang-Young Yoon and Hong-Hyun Park
Toxics 2022, 10(7), 369; https://doi.org/10.3390/toxics10070369 - 4 Jul 2022
Cited by 10 | Viewed by 1946
Abstract
Thiram, an oxidized dimer of dithiocarbamate, has fungicidal and ectoparasiticidal roles. This study aimed to determine the effects of thiram on the development of zebrafish (ZF) embryos. The developmental toxicity test was performed in accordance with the OECD 236 test guidelines, and ZF [...] Read more.
Thiram, an oxidized dimer of dithiocarbamate, has fungicidal and ectoparasiticidal roles. This study aimed to determine the effects of thiram on the development of zebrafish (ZF) embryos. The developmental toxicity test was performed in accordance with the OECD 236 test guidelines, and ZF embryos were subjected to several thiram concentrations and a DMSO (0.01%) control. Subsequently, embryo mortalities and developmental anomalies were evaluated at different hours post fertilization (hpf). Thiram was highly toxic to ZF, with calculated median lethal concentrations (LC50) of thiram at 48 and 96 h as 13.10 ± 2.17 and 8.87 ± 2.09 μg/L, respectively. Thiram-treated embryos/larvae exhibited a variety of deformities, such as abnormal somites, reduced eye pigment, abnormal tail shape, yolk sac edema, hatching defects, and curved spines, with a median effective concentration (EC50) of 3.88 ± 1.23, 5.04 ± 1.82, 6.23 ± 0.92, 5.24 ± 2.22, 1.39 ± 0.25, and 2.60 ± 0.82 μg/L, respectively. Teratogenic index (TI) values ranged from 1.42 to 6.66 for the scored deformities. At 48 hpf, the average heartbeat of the control group was 177.20 ± 5.63 per minute, while the highest thiram-treated group (40 μg/L) was 99.50 ± 18.12 per minute. In addition, cardiac-related issues, such as pericardial edema and abnormal blood flow, were observed in thiram-treated ZF embryos. Overall, these findings suggest that thiram is teratogenic to ZF. Full article
(This article belongs to the Special Issue Zebrafish as a Model for Pharmacological and Toxicological Research)
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12 pages, 6821 KiB  
Article
Environmental Risk Assessment of Dexamethasone Sodium Phosphate and Tocilizumab Mixture in Zebrafish Early Life Stage (Danio rerio)
by Davide Di Paola, Jessica Maria Abbate, Carmelo Iaria, Marika Cordaro, Rosalia Crupi, Rosalba Siracusa, Ramona D’Amico, Roberta Fusco, Daniela Impellizzeri, Salvatore Cuzzocrea, Nunziacarla Spanò, Enrico Gugliandolo and Alessio Filippo Peritore
Toxics 2022, 10(6), 279; https://doi.org/10.3390/toxics10060279 - 25 May 2022
Cited by 17 | Viewed by 2369
Abstract
Pharmaceuticals are widely regarded as a menace to the aquatic environment. The constant consumption of biologically active chemicals for human health has been matched by an increase in the leaking of these compounds in natural habitats over the last two decades. This study [...] Read more.
Pharmaceuticals are widely regarded as a menace to the aquatic environment. The constant consumption of biologically active chemicals for human health has been matched by an increase in the leaking of these compounds in natural habitats over the last two decades. This study was aimed to evaluate the molecular pathway underling the developmental toxicity of exposure in the ecological environment. Zebrafish embryos were exposed at doses of dexamethasone sodium phosphate (DEX) 1 μmol/L, tocilizumab 442.1 μmol/L and dexamethasone + tocilizumab (1 μmol/L and 442.1 μmol/L, respectively) from 24 h post-fertilization (hpf) to 96 hpf. This study confirmed that DEX exposure in association with tocilizumab 442.1 μmol/L at 1 μmol/L (non-toxic concentration) affected the survival and hatching rate, morphology score, and body length. Additionally, it significantly disturbed the antioxidant defense system in zebrafish larvae. Furthermore, a DEX 1 μmol/L and tocilizumab 442.1 μmol/L association also increased the production of apoptosis-related proteins (caspase-3, bax, and bcl-2). Full article
(This article belongs to the Special Issue Zebrafish as a Model for Pharmacological and Toxicological Research)
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