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Pharmaceuticals
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Application of Zebrafish Model in Pharmacology and Toxicology
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Application of Zebrafish Model in Pharmacology and Toxicology

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 15 February 2026 | Viewed by 578

Special Issue Editors

Dr. Geonildo Rodrigo Disner

E-Mail Website
Guest Editor
Plataforma Zebrafish of the Laboratory of Applied Toxinology (CeTICS/FAPESP), Butantan Institute, São Paulo 05503-900, Brazil
Interests: zebrafish; toxicology; microbiome; animal toxins; environmental medicine; one health
Prof. Dr. Mônica Lopes-Ferreira

E-Mail Website
Guest Editor
Plataforma Zebrafish of the Laboratory of Applied Toxinology (CeTICS/FAPESP), Butantan Institute, São Paulo 05503-900, Brazil
Interests: zebrafish; toxicology; drug discovery; animal toxins; scientific dissemination
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to this new Special Issue of the journal Pharmaceuticals, which aims to gather the latest research findings and innovative insights on the use of the zebrafish model in the fields of pharmacology and toxicology.

Over the past decades, zebrafish have emerged as a remarkably versatile alternative model, helping scientists uncover toxicological, cellular, and molecular aspects of drugs under development, pharmaceutical degradation products—within the body and in the ecosystems– and environmental toxicants that form part of the human exposome.

Thanks to key advantages such as rapid development, high fecundity (enabling high-throughput screening), optical transparency, and high genetic homology to humans, zebrafish have proven invaluable in pharmacology and toxicology research. These endeavors support advances in drug development pipelines, regulation of discarded pollutants, and the elucidation of the mechanisms of action of chemical substances that impact human, animal, and environmental health.

Looking towards promoting and expanding the application of the zebrafish model in the areas of pharmacology and toxicology, this Special Issue aims to publish high-quality contributions—including original research and review articles—covering, but not limited to, the following topics:

  • Drug discovery and development;
  • High-throughput screening of pharmaceutical compounds;
  • Behavioral pharmacology;
  • Zebrafish to model human diseases for drug screening;
  • Preclinical safety and efficacy assessments;
  • Investigations of drug-induced organ toxicity;
  • Developmental and reproductive toxicity;
  • Assessment of endocrine-disrupting chemicals;
  • Pharmacokinetics and drug metabolism in zebrafish;
  • Microbiome-drug interaction studies;
  • Evaluation of environmental toxicants and pollutants;
  • Omics approaches in zebrafish pharmacology and toxicology;
  • CRISPR/Cas9-based gene editing in zebrafish for target validation.

We are looking forward to receiving your submission.

Dr. Geonildo Rodrigo Disner
Prof. Dr. Mônica Lopes-Ferreira
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 250 words) can be sent to the Editorial Office for assessment.

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. Pharmaceuticals 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 2900 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

  • chemical safety assessment
  • translational research
  • drug screening
  • human exposome
  • environmental contaminants

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (2 papers)

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Research

14 pages, 1025 KB  
Article
Distinct Swimming Behavioral Phenotypes Following Serotonin and Dopamine Transporter Modulation in the Adult Zebrafish Novel Tank Diving Test (NTT)
by Amaury Farías-Cea, Lisandra Pérez, Cristóbal Leal, Kerim Segura, Valentina Hernández, Caridad Atiés-Pérez, Luis Miguel Martínez, Martin Hödar-Salazar, Miguel Reyes-Parada, Ramón Sotomayor-Zárate, Francisca Rojas-Hidalgo, Marcela Julio-Pieper, Javier A. Bravo, Dasiel O. Borroto-Escuela and Patricio Iturriaga-Vásquez
Pharmaceuticals 2025, 18(12), 1807; https://doi.org/10.3390/ph18121807 - 27 Nov 2025
Abstract
Background/Objective: Serotonin and dopamine are key neurotransmitters involved in regulating mood, anxiety, and locomotor activity. Specific transporters mediate their reuptake, SERT and DAT, making them targets for drugs such as Fluoxetine and Methylphenidate. Zebrafish (Danio rerio), due to their genetic and [...] Read more.
Background/Objective: Serotonin and dopamine are key neurotransmitters involved in regulating mood, anxiety, and locomotor activity. Specific transporters mediate their reuptake, SERT and DAT, making them targets for drugs such as Fluoxetine and Methylphenidate. Zebrafish (Danio rerio), due to their genetic and neurochemical similarity to humans, serve as a valuable model for studying the behavioral effects of these drugs. This study aimed to compare the behavioral phenotypes induced by SERT and DAT blockers in adult zebrafish using the Novel Tank Diving Test (NTT), thereby generating a swimming profile for drugs acting on these monoamine transporters that can be utilized in drug discovery and behavior. Methods: Adult zebrafish were administered Fluoxetine or Methylphenidate and subjected to the NTT. Behavioral endpoints measured included bottom-dwelling time (anxiety-like behavior), swimming velocity (locomotor activity), and transitions to the upper zone (exploratory behavior). Results: Fluoxetine treatment significantly reduced bottom-dwelling behavior, increased transitions to the upper zone, and decreased erratic swimming, indicating reduced anxiety and enhanced exploration. In contrast, Methylphenidate administration led to prolonged bottom-dwelling and reduced exploration, suggesting increased anxiety-like behavior and decreased exploration. These findings highlight distinct behavioral profiles resulting from selective modulation of serotonergic and dopaminergic pathways. Conclusions: The study demonstrates that SERT and DAT blockades produce divergent behavioral effects in adult zebrafish, with Fluoxetine exhibiting anxiolytic and exploratory-promoting actions. At the same time, Methylphenidate induces anxiety-like and less exploratory behaviors. These results underscore the utility of zebrafish as a valuable translational model for neuropharmacological research and drug discovery, providing insights into the differential impact of serotonergic and dopaminergic modulation on behavior. Full article
(This article belongs to the Special Issue Application of Zebrafish Model in Pharmacology and Toxicology)
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17 pages, 3168 KB  
Article
Bisphenol A Alters the Expression of Genes Involved in Lipogenesis, Inflammation, and Oxidative Stress in the Liver of Adult Zebrafish
by Eronides Anathan de Heberle Salau, Daniela Diglio, Giuliano Rizzotto Guimarães, Orlando Vieira Furtado-Filho and Marilene Porawski
Pharmaceuticals 2025, 18(11), 1765; https://doi.org/10.3390/ph18111765 - 20 Nov 2025
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Abstract
Background: Bisphenol A (BPA) is a widespread environmental endocrine disruptor associated with metabolic dysfunction-associated steatotic liver disease (MASLD). However, its short-term effects at low, environmentally relevant concentrations are still poorly understood. Methods: Adult zebrafish were exposed to 5, 20, or 100 µg/L BPA [...] Read more.
Background: Bisphenol A (BPA) is a widespread environmental endocrine disruptor associated with metabolic dysfunction-associated steatotic liver disease (MASLD). However, its short-term effects at low, environmentally relevant concentrations are still poorly understood. Methods: Adult zebrafish were exposed to 5, 20, or 100 µg/L BPA for 48 h, 7, or 14 days in a pilot test. The lowest effective condition (20 µg/L for 7 days) was selected for a complete experiment. Fish were divided into two groups: control and BPA-exposed (n = 50/group). After exposure, livers were collected for histological (HE, Oil Red O, Nile Red) and molecular (RT-qPCR) analyses. Results: Exposure to 20 µg/L BPA for 7 days induced moderate to severe hepatic steatosis, characterized by vacuolization, hepatocyte ballooning, and lipid accumulation. Gene expression analysis showed upregulation of fasn (fatty acid synthase), acc1 (acetyl-CoA carboxylase 1), srebp-1c (sterol regulatory element-binding protein 1c), nfkb (nuclear factor kappa B), il-6 (interleukin-6), gpx1 (glutathione peroxidase 1), sod (superoxide dismutase), cyp1a (cytochrome P450 1A), and cyp2ad2 (cytochrome P450 2AD2), while adipor2 (adiponectin receptor 2) and gpx4 (glutathione peroxidase 4) were downregulated (decreased activity). Conclusions: Short-term exposure to a low, environmentally relevant concentration of BPA was sufficient to trigger hepatic steatosis in zebrafish. These effects were associated with enhanced lipogenesis, inflammation, oxidative imbalance, and altered xenobiotic metabolism, suggesting that even brief, low-dose BPA exposure may contribute to early events in MASLD pathogenesis. Full article
(This article belongs to the Special Issue Application of Zebrafish Model in Pharmacology and Toxicology)
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