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Zebrafish Models in Toxicology and Disease Studies

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 10443

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Special Issue Editor

Dr. Ida Ferrandino

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Guest Editor

Department of Biology, University of Naples “Federico II”, via Cinthia 21, 80126 Naples, Italy
Interests: environmental toxicity; glia; nervous system; endocrine system; pituitary gland; neuroinflammation/degeneration; neuroendocrine diseases; metals; cadmium; aluminum; food additives; zebrafish; comparative anatomy; cell and molecular biology; histology; immunohistochemistry; cell death; behavioral tests; genotoxicity; oxidative stress; embryonic development

Special Issue Information

Dear Colleagues,

Zebrafish is a well-known model organism in a variety of biological disciplines. In recent years, zebrafish are increasingly used in basic and applied research, including medicine, toxicology, and environmental science. This freshwater fish is also employed to test the toxicity of chemicals. Considering the link between toxic chemical exposures and various diseases, such as neurodegenerative ones, zebrafish has become a good experimental model to study the effects of natural and synthetic contaminants on human health so and on the environment in general.

This Special Issue focuses on original research articles and reviews to report the significant contribution to employing zebrafish to study the molecular and cellular mechanisms of the harmful action of known but also emerging contaminants, associated with different human diseases, or drugs. Studies on embryos, larvae, mature fish or multigenerational effects are invited. Potential topics include the study of toxics or suspected substances classified mainly as endocrine disruptors, metals, and organic pollutants, but not limited, to the base of important and diffuse neurologic and endocrine disorders.

Dr. Ida Ferrandino
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
environmental toxicology
human health
chemicals
pollutions
cell biology
glia
neurotoxicology
endocrine toxicology
neurodegeneretion

Published Papers (6 papers)

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Research

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8 pages, 1681 KiB

Open AccessCommunication

Exploring Embryo-Ototoxic Effects: Insights into Deodorant-Induced Hair Cell Damage in Zebrafish

by Hee Soo Yoon, Kyung Tae Hyun, Sumin Hong, Saemi Park, Eunjung Han, Hyun woo Baek, Yun Kyoung Lee, Kang Hyeon Lim, Yoon Chan Rah and June Choi

Int. J. Mol. Sci. 2024, 25(2), 948; https://doi.org/10.3390/ijms25020948 - 12 Jan 2024

Viewed by 675

Abstract

Our study investigated the embryo-ototoxic effects of deodorant2 (DA2) on zebrafish embryos, which serve as valuable model organisms due to genetic and physiological similarities to humans. We focused on understanding DA2’s impact on zebrafish hair cells, which are vital for sensory perception and balance regulation. DA2, provided by the Ministry of Environment, Republic of Korea, was used at 460 μg/mL in dimethyl sulfoxide (DMSO), with a 0.43% DMSO solvent control group. Three experiments, each using 10 zebrafish specimens from each group, showed an initial 13% hair cell count reduction in the DA2-exposed group. Subsequent experiments demonstrated reductions of 37% and 22%, each with one mortality case. Statistical analysis revealed a significant 24% hair cell count reduction in the DA2-exposed group. We also assessed DA2’s impact on zebrafish behavior. Although not statistically significant, differences in distances traveled (0.33–0.39, 95% confidence interval: −0.46–1.1, p = 0.2033) and latencies (−0.016–0.018, 95% confidence interval: −0.052–0.021, p = 0.1917) hinted at negative effects. These results highlight DA2’s ototoxic properties affecting zebrafish auditory systems and behavior. Further investigation into DA2’s effects on aquatic organisms and potential mitigation strategies are essential. These findings contribute to understanding DA2’s safety profile, benefiting aquatic ecosystems and human health assessments. Full article

(This article belongs to the Special Issue Zebrafish Models in Toxicology and Disease Studies)

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13 pages, 1637 KiB

Open AccessArticle

Synthesis and Degradation of Poly(ADP-ribose) in Zebrafish Brain Exposed to Aluminum

by Anna Rita Bianchi, Alessandra La Pietra, Valeria Guerretti, Anna De Maio, Teresa Capriello and Ida Ferrandino

Int. J. Mol. Sci. 2023, 24(10), 8766; https://doi.org/10.3390/ijms24108766 - 15 May 2023

Cited by 1 | Viewed by 1507

Abstract

Poly(ADPribosyl)ation is a post-translational protein modification, catalyzed by poly(ADP-ribose) polymerase (PARPs) enzymes, responsible for ADP-ribose polymer synthesis (PAR) from NAD⁺. PAR turnover is assured by poly(ADPR) glycohydrolase (PARGs) enzymes. In our previous study, the altered histology of zebrafish brain tissue, resulting in demyelination and neurodegeneration also with poly(ADPribosyl)ation hyperactivation, was demonstrated after aluminum (Al) exposure for 10 and 15 days. On the basis of this evidence, the aim of the present research was to study the synthesis and degradation of poly(ADP-ribose) in the brain of adult zebrafish exposed to 11 mg/L of Al for 10, 15, and 20 days. For this reason, PARP and PARG expression analyses were carried out, and ADPR polymers were synthesized and digested. The data showed the presence of different PARP isoforms, among which a human PARP1 counterpart was also expressed. Moreover, the highest PARP and PARG activity levels, responsible for the PAR production and its degradation, respectively, were measured after 10 and 15 days of exposure. We suppose that PARP activation is related to DNA damage induced by Al, while PARG activation is needed to avoid PAR accumulation, which is known to inhibit PARP and promote parthanatos. On the contrary, PARP activity decrease at longer exposure times suggests that neuronal cells could adopt the stratagem of reducing polymer synthesis to avoid energy expenditure and allow cell survival. Full article

(This article belongs to the Special Issue Zebrafish Models in Toxicology and Disease Studies)

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Graphical abstract

18 pages, 3171 KiB

Open AccessArticle

First Identification of a Large Set of Serine Hydrolases by Activity-Based Protein Profiling in Dibutyl Phthalate-Exposed Zebrafish Larvae

by Rodrigue S. Yedji, Bénédicte Sohm, Virginie Salnot, François Guillonneau, Carole Cossu-Leguille and Eric Battaglia

Int. J. Mol. Sci. 2022, 23(24), 16060; https://doi.org/10.3390/ijms232416060 - 16 Dec 2022

Viewed by 1555

Abstract

Despite the involvement of several serine hydrolases (SHs) in the metabolism of xenobiotics such as dibutyl phthalate (DBP), no study has focused on mapping this enzyme class in zebrafish, a model organism frequently used in ecotoxicology. Here, we survey and identify active SHs in zebrafish larvae and search for biological markers of SH type after exposure to DBP. Zebrafish were exposed to 0, 5, and 100 µg/L DBP from 4 to 120 h post-fertilization. A significant decrease in vitellogenin expression level of about 2-fold compared to the control was found in larvae exposed to 100 µg/L DBP for 120 h. The first comprehensive profiling of active SHs in zebrafish proteome was achieved with an activity-based protein profiling (ABPP) approach. Among 49 SHs identified with high confidence, one was the carboxypeptidase ctsa overexpressed in larvae exposed to 100 µg/L DBP for 120 h. To the best of our knowledge, this is the first time that a carboxypeptidase has been identified as deregulated following exposure to DBP. The overall results indicate that targeted proteomics approaches, such as ABPP, can, therefore, be an asset for understanding the mechanism of action related to xenobiotics in ecotoxicology. Full article

(This article belongs to the Special Issue Zebrafish Models in Toxicology and Disease Studies)

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13 pages, 1986 KiB

Open AccessArticle

Size-Dependent Effects of Polystyrene Nanoparticles (PS-NPs) on Behaviors and Endogenous Neurochemicals in Zebrafish Larvae

by Kyu-Seok Hwang, Yuji Son, Seong Soon Kim, Dae-Seop Shin, So Hee Lim, Jung Yoon Yang, Ha Neul Jeong, Byung Hoi Lee and Myung Ae Bae

Int. J. Mol. Sci. 2022, 23(18), 10682; https://doi.org/10.3390/ijms231810682 - 14 Sep 2022

Cited by 16 | Viewed by 2215

Abstract

Microplastics, small pieces of plastic derived from polystyrene, have recently become an ecological hazard due to their toxicity and widespread occurrence in aquatic ecosystems. In this study, we exposed zebrafish larvae to two types of fluorescent polystyrene nanoparticles (PS-NPs) to identify their size-dependent effects. PS-NPs of 50 nm, unlike 100 nm PS-NPs, were found to circulate in the blood vessels and accumulate in the brains of zebrafish larvae. Behavioral and electroencephalogram (EEG) analysis showed that 50 nm PS-NPs induce abnormal behavioral patterns and changes in EEG power spectral densities in zebrafish larvae. In addition, the quantification of endogenous neurochemicals in zebrafish larvae showed that 50 nm PS-NPs disturb dopaminergic metabolites, whereas 100 nm PS-NPs do not. Finally, we assessed the effect of PS-NPs on the permeability of the blood–brain barrier (BBB) using a microfluidic system. The results revealed that 50 nm PS-NPs have high BBB penetration compared with 100 nm PS-NPs. Taken together, we concluded that small nanoparticles disturb the nervous system, especially dopaminergic metabolites. Full article

(This article belongs to the Special Issue Zebrafish Models in Toxicology and Disease Studies)

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17 pages, 2035 KiB

Open AccessArticle

SGLT2 Inhibitor Empagliflozin Modulates Ion Channels in Adult Zebrafish Heart

by Alexey V. Karpushev, Valeria B. Mikhailova, Ekaterina S. Klimenko, Alexander N. Kulikov, Dmitry Yu. Ivkin, Elena Kaschina and Sergey V. Okovityi

Int. J. Mol. Sci. 2022, 23(17), 9559; https://doi.org/10.3390/ijms23179559 - 23 Aug 2022

Cited by 5 | Viewed by 2225

Abstract

Empagliflozin, an inhibitor of sodium-glucose co-transporter 2 (iSGLT2), improves cardiovascular outcomes in patients with and without diabetes and possesses an antiarrhythmic activity. However, the mechanisms of these protective effects have not been fully elucidated. This study aimed to explore the impact of empagliflozin on ion channel activity and electrophysiological characteristics in the ventricular myocardium. The main cardiac ionic currents (I_Na, I_CaL, I_CaT, I_Kr, I_Ks) and action potentials (APs) were studied in zebrafish. Whole-cell currents were measured using the patch clamp method in the isolated ventricular cardiomyocytes. The conventional sharp glass microelectrode technique was applied for the recording of APs from the ventricular myocardium of the excised heart. Empagliflozin pretreatment compared to the control group enhanced potassium I_Kr step current density in the range of testing potentials from 0 to +30 mV, I_Kr tail current density in the range of testing potentials from +10 to +70 mV, and I_Ks current density in the range of testing potentials from −10 to +20 mV. Moreover, in the ventricular myocardium, empagliflozin pretreatment shortened AP duration APD as shown by reduced APD50 and APD90. Empagliflozin had no influence on sodium (I_Na) and L- and T-type calcium currents (I_CaL and I_CaT) in zebrafish ventricular cardiomyocytes. Thus, we conclude that empagliflozin increases the rapid and slow components of delayed rectifier K⁺ current (I_Kr and I_Ks). This mechanism could be favorable for cardiac protection. Full article

(This article belongs to the Special Issue Zebrafish Models in Toxicology and Disease Studies)

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Review

Jump to: Research

19 pages, 1540 KiB

Open AccessReview

Zebrafish (Danio rerio) as a Model for the Study of Developmental and Cardiovascular Toxicity of Electronic Cigarettes

by Eman Hussen, Nada Aakel, Abdullah A. Shaito, Maha Al-Asmakh, Haissam Abou-Saleh and Zain Z. Zakaria

Int. J. Mol. Sci. 2024, 25(1), 194; https://doi.org/10.3390/ijms25010194 - 22 Dec 2023

Viewed by 1351

Abstract

The increasing popularity of electronic cigarettes (e-cigarettes) as an alternative to conventional tobacco products has raised concerns regarding their potential adverse effects. The cardiovascular system undergoes intricate processes forming the heart and blood vessels during fetal development. However, the precise impact of e-cigarette smoke and aerosols on these delicate developmental processes remains elusive. Previous studies have revealed changes in gene expression patterns, disruptions in cellular signaling pathways, and increased oxidative stress resulting from e-cigarette exposure. These findings indicate the potential for e-cigarettes to cause developmental and cardiovascular harm. This comprehensive review article discusses various aspects of electronic cigarette use, emphasizing the relevance of cardiovascular studies in Zebrafish for understanding the risks to human health. It also highlights novel experimental approaches and technologies while addressing their inherent challenges and limitations. Full article

(This article belongs to the Special Issue Zebrafish Models in Toxicology and Disease Studies)

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