Zebrafish disease models in drug discovery: from preclinical modelling to clinical trials

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(8), P. 611 - 628

Published: June 11, 2021

Language: Английский

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Phenotypic drug discovery: recent successes, lessons learned and new directions

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(12), P. 899 - 914

Published: May 30, 2022

Language: Английский

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Advanced Functional Nanostructures based on Magnetic Iron Oxide Nanomaterials for Water Remediation: A Review

Water Research, Journal Year: 2020, Volume and Issue: 190, P. 116693 - 116693

Published: Nov. 30, 2020

Language: Английский

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Zebrafish as a Successful Animal Model for Screening Toxicity of Medicinal Plants

Plants, Journal Year: 2020, Volume and Issue: 9(10), P. 1345 - 1345

Published: Oct. 12, 2020

The zebrafish (Danio rerio) is used as an embryonic and larval model to perform in vitro experiments developmental toxicity studies. Zebrafish may be determine the of samples early screening assays, often a high-throughput manner. embryotoxicity at leading edge toxicology research due short time required for analyses, transparency embryos, life cycle, high fertility, genetic data similarity. studies range from assessing bioactive compounds or crude extracts plants determining optimal process. Most studied were polar, such ethanol, methanol, aqueous solutions, which detect bioactivity. This review examines latest using study highlights its power tool detecting medicinal effectiveness enhancing understanding new drug generation. goal this was develop link ethnopharmacological that can by other researchers conduct future research.

Language: Английский

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Zebrafish as a tractable model of human cardiovascular disease

British Journal of Pharmacology, Journal Year: 2021, Volume and Issue: 179(5), P. 900 - 917

Published: March 31, 2021

Mammalian models including non-human primates, pigs and rodents have been used extensively to study the mechanisms of cardiovascular disease. However, there is an increasing desire for alternative model systems that provide excellent scientific value while replacing or reducing use mammals. Here, we review zebrafish, Danio rerio, development The anatomy physiology zebrafish mammalian are compared, describe in studying cardiac (e.g. congenital heart defects, cardiomyopathy, conduction disorders regeneration) vascular (endothelial dysfunction atherosclerosis, lipid metabolism, ageing, neurovascular stroke) pathologies. We also pharmacological responses drugs several features make them a compelling vivo screening compounds treatment LINKED ARTICLES: This article part themed issue on Preclinical Models Cardiovascular disease research (BJP 75th Anniversary). To view other articles this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc.

Language: Английский

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Zebrafish Larvae Behavior Models as a Tool for Drug Screenings and Pre-Clinical Trials: A Review

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(12), P. 6647 - 6647

Published: June 14, 2022

To discover new molecules or review the biological activity and toxicity of therapeutic substances, drug development, research relies on robust systems to obtain reliable results. Phenotype-based screenings can transpose organism’s compensatory pathways by adopting multi-target strategies for treating complex diseases, zebrafish emerged as an important model biomedical screenings. Zebrafish’s clear correlation between neuro-anatomical physiological features behavior is very similar that verified in mammals, enabling construction relevant experimental models neurological disorders research. Zebrafish presents highly conserved are found higher vertebrates, including along with a behavioral repertoire. Moreover, it sensitive pharmacological/environmental manipulations, these phenotypes detected both larvae adults. These advantages align 3Rs concept qualify powerful tool pre-clinical trials. This highlights domains studied their neurotransmitter summarizes currently used techniques evaluate quantify laboratory studies.

Language: Английский

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Attenuation of Lipopolysaccharide-Induced Inflammatory Responses through Inhibition of the NF-κB Pathway and the Increased NRF2 Level by a Flavonol-Enriched n-Butanol Fraction from Uvaria alba

ACS Omega, Journal Year: 2023, Volume and Issue: 8(6), P. 5377 - 5392

Published: Jan. 31, 2023

Pathologic hyperreactive inflammatory responses occur when there is excessive activation of a proinflammatory NF-κB pathway and reduced cytoprotective NRF2 cascade. The noncytotoxic, highly selective COX-2 inhibitory flavonol-enriched butanol fraction (UaB) from Uvaria alba (U. alba) was investigated for its modulating potential by targeting activity. Enzyme-linked immunosorbent assay initially performed to measure levels mediators [nitric oxide (NO), prostaglandin E2, reactive oxygen species (ROS)] cytokines [tumor necrosis factor-alpha (TNF-α), IL-1β, IL-6], followed reverse transcription-polymerase chain reaction western blotting determine mRNA protein expression, respectively. Using immunofluorescence staining combined with blot analysis, the further investigated. activity also measured using luciferase reporter assay. UaB abrogated expressions inducible nitric synthase (iNOS), COX-2, TNF-α, IL-6 in RAW 264.7 macrophages, thereby suppressing production cytokines. This validated concentration-dependent decrease NO ROS observed zebrafish (Danio rerio) larvae. increased HaCaT/ARE cell line attenuated inhibiting nuclear translocation transcription factor p65 macrophages. Nontargeted LC-MS analysis revealed presence flavonols quercitrin (1), quercetin (2), rutin (3), kaempferol (4), 3-O-rutinoside (5). Molecular docking indicates that major flavonol aglycones have high affinity toward NSAID-binding sites, TNF-α converting enzyme, while glycosylated flavonoids showed strong binding iNOS IKK-all possessing dynamic stability performing molecular dynamics simulations at 140 ns. first report elucidated mechanistic anti-inflammatory Philippine endemic plant U. alba.

Language: Английский

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The posterity of Zebrafish in paradigm of in vivo molecular toxicological profiling

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116160 - 116160

Published: Jan. 21, 2024

The aggrandised advancement in utility of advanced day-to-day materials and nanomaterials has raised serious concern on their biocompatibility with human other biotic members. In last few decades, understanding toxicity these been given the centre stage research using many vitro vivo models. Zebrafish (Danio rerio), a freshwater fish member minnow family garnered much attention due to its distinct features, which make it an important frequently used animal model various fields embryology toxicological studies. Given that fertilization development zebrafish eggs take place externally, they serve as excellent organism for studying early developmental stages. Moreover, possess comparable genetic composition humans share almost 70% genes mammals. This particular become increasingly popular, especially research. serves link between studies analysis It is appealing choice vertebrate research, when employing high-throughput methods, small size, swift development, relatively affordable laboratory setup. enhanced comprehension pathobiology drug toxicity. review emphasizes recent developments screening assays, new insights gained about drugs through assays. Specifically, cardio, neural, and, hepatic toxicology inferred by applications nanoparticles have highlighted.

Language: Английский

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Approaches to Test the Neurotoxicity of Environmental Contaminants in the Zebrafish Model: From Behavior to Molecular Mechanisms

Environmental Toxicology and Chemistry, Journal Year: 2020, Volume and Issue: 40(4), P. 989 - 1006

Published: Dec. 3, 2020

Abstract The occurrence of neuroactive chemicals in the aquatic environment is on rise and poses a potential threat to biota currently unpredictable outcome. In particular, subtle changes caused by these an organism's sensation or behavior are difficult tackle with current test systems that focus rodents vitro omit whole‐animal responses. recent years, zebrafish ( Danio rerio ) has become popular model organism for toxicological studies testing strategies, such as standardized use early life stages Organisation Economic Co‐operation Development's guideline 236. terms neurotoxicity, provides powerful investigate nervous system from several different angles, offering ability mechanisms action detail. mechanistic understanding gained through analysis this species good basic knowledge how might interact teleost system. Such information can help infer effects occurring other exposed their predicting risks chemical ecosystem. present article, we highlight approaches ranging behavioral structural, functional, molecular larval system, providing holistic view neurotoxic outcomes. Environ Toxicol Chem 2021;40:989–1006. © 2020 SETAC

Language: Английский

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Zebrafish Embryos and Larvae as Alternative Animal Models for Toxicity Testing

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(24), P. 13417 - 13417

Published: Dec. 14, 2021

Prerequisite to any biological laboratory assay employing living animals is consideration about its necessity, feasibility, ethics and the potential harm caused during an experiment. The imperative of these thoughts has led formulation 3R-principle, which today a pivotal scientific standard animal experimentation worldwide. rising amount investigations utilizing throughout last decades, either for regulatory concerns or basic science, demands development alternative methods in accordance with 3R help reduce experiments mammals. This demand resulted investigation additional vertebrate species displaying favourable properties. One prominent among zebrafish (Danio rerio), as small ray-finned fish are well established science feature outstanding characteristics. In this review, we highlight advantages general prerequisites embryos larvae before free-feeding stages toxicological testing, particular focus on cardio-, neuro, hepato- nephrotoxicity. Furthermore, discuss toxicokinetics, current advances organ toxicity testing how advanced (such automation, imaging genetic techniques) can refine future studies species.

Language: Английский

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