scholarly journals Establishment of a rotavirus-infected zebrafish model and its application in drug screening

2022 ◽  
Vol 145 ◽  
pp. 112398
Author(s):  
Lijun Song ◽  
Xuemei Zhu ◽  
Yujing Zhou ◽  
Yuxuan Feng ◽  
Guiqin Dai ◽  
...  
Keyword(s):  
Drug Screening ◽  
Zebrafish Model

scholarly journals Testing Tuberculosis Drug Efficacy in a Zebrafish High-Throughput Translational Medicine Screen

2014 ◽  
Vol 59 (2) ◽  
pp. 753-762 ◽  
Author(s):  
Anita Ordas ◽  
Robert-Jan Raterink ◽  
Fraser Cunningham ◽  
Hans J. Jansen ◽  
Malgorzata I. Wiweger ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Drug Efficacy ◽  
Drug Uptake ◽  
Spectrometric Analysis ◽  
Major Advance ◽  
Zebrafish Model ◽  
Content Type ◽  
Screening Platform

ABSTRACTThe translational value of zebrafish high-throughput screens can be improved when more knowledge is available on uptake characteristics of potential drugs. We investigated reference antibiotics and 15 preclinical compounds in a translational zebrafish-rodent screening system for tuberculosis. As a major advance, we have developed a new tool for testing drug uptake in the zebrafish model. This is important, because despite the many applications of assessing drug efficacy in zebrafish research, the current methods for measuring uptake using mass spectrometry do not take into account the possible adherence of drugs to the larval surface. Our approach combines nanoliter sampling from the yolk using a microneedle, followed by mass spectrometric analysis. To date, no single physicochemical property has been identified to accurately predict compound uptake; our method offers a great possibility to monitor how any novel compound behaves within the system. We have correlated the uptake data with high-throughput drug-screening data fromMycobacterium marinum-infected zebrafish larvae. As a result, we present an improved zebrafish larva drug-screening platform which offers new insights into drug efficacy and identifies potential false negatives and drugs that are effective in zebrafish and rodents. We demonstrate that this improved zebrafish drug-screening platform can complement conventional models ofin vivoMycobacterium tuberculosis-infected rodent assays. The detailed comparison of two vertebrate systems, fish and rodent, may give more predictive value for efficacy of drugs in humans.

scholarly journals From Omics to Drug Metabolism and High Content Screen of Natural Product in Zebrafish: A New Model for Discovery of Neuroactive Compound

2012 ◽  
Vol 2012 ◽  
pp. 1-20 ◽  
Author(s):  
Ming Wai Hung ◽  
Zai Jun Zhang ◽  
Shang Li ◽  
Benson Lei ◽  
Shuai Yuan ◽  
...  
Keyword(s):  
Drug Metabolism ◽  
Drug Screening ◽  
Environmental Science ◽  
Pharmacological Action ◽  
Zebrafish Model ◽  
Lead Compounds ◽  
Efficacy Parameters

The zebrafish (Danio rerio) has recently become a common model in the fields of genetics, environmental science, toxicology, and especially drug screening. Zebrafish has emerged as a biomedically relevant model forin vivohigh content drug screening and the simultaneous determination of multiple efficacy parameters, including behaviour, selectivity, and toxicity in the content of the whole organism. A zebrafish behavioural assay has been demonstrated as a novel, rapid, and high-throughput approach to the discovery of neuroactive, psychoactive, and memory-modulating compounds. Recent studies found a functional similarity of drug metabolism systems in zebrafish and mammals, providing a clue with why some compounds are active in zebrafishin vivobut notin vitro, as well as providing grounds for the rationales supporting the use of a zebrafish screen to identify prodrugs. Here, we discuss the advantages of the zebrafish model for evaluating drug metabolism and the mode of pharmacological action with the emerging omics approaches. Why this model is suitable for identifying lead compounds from natural products for therapy of disorders with multifactorial etiopathogenesis and imbalance of angiogenesis, such as Parkinson's disease, epilepsy, cardiotoxicity, cerebral hemorrhage, dyslipidemia, and hyperlipidemia, is addressed.

scholarly journals Drug screening in a zebrafish model of Duchenne muscular dystrophy

2011 ◽  
Vol 108 (13) ◽  
pp. 5331-5336 ◽  
Author(s):  
G. Kawahara ◽  
J. A. Karpf ◽  
J. A. Myers ◽  
M. S. Alexander ◽  
J. R. Guyon ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Drug Screening ◽  
Zebrafish Model

scholarly journals Targeting the Redox Balance Pathway Using Ascorbic Acid in sdhb Zebrafish Mutant Larvae

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5124
Author(s):  
Margo Dona ◽  
Maaike Lamers ◽  
Svenja Rohde ◽  
Marnix Gorissen ◽  
Henri J. L. M. Timmers
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
Drug Screening ◽  
Redox Balance ◽  
Wild Type ◽  
Zebrafish Model ◽  
High Throughput Drug Screening ◽  
Anti Cancer ◽  
Cancer Agent

Patients with mutations in the β-subunit of the succinate dehydrogenase (SDHB) have the highest risk to develop incurable malignant phaeochromocytomas and paragangliomas (PPGLs). Therapy development is hindered by limited possibilities to test new therapeutic strategies in vivo. One possible molecular mechanism of SDHB-associated tumorigenesis originates in an overproduction of reactive oxygen species (ROS) due to mitochondrial dysfunction. Ascorbic acid (Vitamin C) has already been shown to act as anti-cancer agent in several clinical trials for various types of cancer. In this study, the potential of the sdhbrmc200 zebrafish model to study SDHB-associated PPGLs using a drug screening approach was investigated. First, we identified increased basal ROS levels in homozygous sdhb larvae compared to heterozygous and wild-type siblings. Using a semi high-throughput drug screening, the effectiveness of different dosages of anti- and pro-oxidant Vitamin C were assessed to evaluate differences in survival, ROS levels, and locomotor activity. Low-dosage levels of Vitamin C induced a decrease of ROS levels but no significant effects on lifespan. In contrast, high-dosage levels of Vitamin C shortened the lifespan of the homozygous sdhbrmc200 larvae while not affecting the lifespan of heterozygous and wild-type siblings. These results validated the sdhbrmc200 zebrafish model as a powerful drug screening tool that may be used to identify novel therapeutic targets for SDHB-associated PPGLs.

scholarly journals Development of a Zebrafish Model for Rapid Drug Screening against Alzheimer’s Disease

2016 ◽  
Vol 4 (4) ◽  
Author(s):  
Wenhai Huang ◽  
Chuansheng Li ◽  
Zhengrong Shen ◽  
Xiaoyu Zhu ◽  
Bo Xia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Screening ◽  
Zebrafish Model

scholarly journals Alexander Disease Modeling in Zebrafish: An In Vivo System Suitable to Perform Drug Screening

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1490
Author(s):  
Simona Candiani ◽  
Silvia Carestiato ◽  
Andreas F. Mack ◽  
Daniele Bani ◽  
Matteo Bozzo ◽  
...  
Keyword(s):  
Heat Shock ◽  
Drug Screening ◽  
Disease Modeling ◽  
De Novo ◽  
Alexander Disease ◽  
Glial Fibrillary Acid Protein ◽  
Suitable Model ◽  
Zebrafish Model ◽  
In Vivo Models

Alexander disease (AxD) is a rare astrogliopathy caused by heterozygous mutations, either inherited or arising de novo, on the glial fibrillary acid protein (GFAP) gene (17q21). Mutations in the GFAP gene make the protein prone to forming aggregates which, together with heat-shock protein 27 (HSP27), αB-crystallin, ubiquitin, and proteasome, contribute to form Rosenthal fibers causing a toxic effect on the cell. Unfortunately, no pharmacological treatment is available yet, except for symptom reduction therapies, and patients undergo a progressive worsening of the disease. The aim of this study was the production of a zebrafish model for AxD, to have a system suitable for drug screening more complex than cell cultures. To this aim, embryos expressing the human GFAP gene carrying the most severe p.R239C under the control of the zebrafish gfap gene promoter underwent functional validation to assess several features already observed in in vitro and other in vivo models of AxD, such as the localization of mutant GFAP inclusions, the ultrastructural analysis of cells expressing mutant GFAP, the effects of treatments with ceftriaxone, and the heat shock response. Our results confirm that zebrafish is a suitable model both to study the molecular pathogenesis of GFAP mutations and to perform pharmacological screenings, likely useful for the search of therapies for AxD.

Development of a vestibular schwannoma xenograft zebrafish model for in vivo antitumor drug screening

2016 ◽  
Vol 126 (12) ◽  
pp. E409-E415 ◽  
Author(s):  
Hyun-Jin Lee ◽  
Yeon Ju Yang ◽  
Sewon Jeong ◽  
Jong Dae Lee ◽  
Seok-Yong Choi ◽  
...  
Keyword(s):  
Vestibular Schwannoma ◽  
Drug Screening ◽  
Antitumor Drug ◽  
Zebrafish Model
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