The virtual heart as a platform for screening drug cardiotoxicity

Yuan, Ye; Bai, Xiangyun; Luo, Cunjin; Wang, Kuanquan; Zhang, Henggui

doi:10.1111/bph.12996

Cited by 39 publications

(26 citation statements)

References 97 publications

(146 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The emergence of zebrafish as a model for assessing cardio-neuro-or geno-toxicity of drugs is reflective of its advantages over other animal models with respect to the principles of the 3Rs (replacement, reduction and refinement). On the other hand, the ease of genome editing, using new mutagenesis techniques such as CRISPR/Cas9 [79] (in the fish, will make suitable future studies to pair human genetic mutations with their molecular functions.…”

Section: Resultsmentioning

confidence: 99%

“…Despite their usefulness, these strategies do not provide enough information about toxicity in the organism as an effect of the secondary metabolism derived from drugs, or the drug effects in other cellular lines present in the heart [76][77][78][79] . Primary cardiomyocytes derived from human embryonic stem cells [78] are used to evaluate cardiotoxicity; however the general consensus is that a reliable in vivo model is needed.…”

Section: Cardiotoxicity Of Small Molecules: Drug Screening Using the mentioning

confidence: 99%

“…Additionally some in silico approaches (computational techniques) can assess the ionic flow by the action of a drug, reaching some results about Na + , K + , L-type Ca 2+ channels or multiple membrane ion channels in cardiomyocytes. These computational models show up as cardiotoxicological method to evaluate the actions of drugs on cardiac electrical activities at cellular and tissue [79] . Cardiac electrophysiology and modeling drug-channel studies, have documented many improvements in the last decades, although, the generation of a virtual heart model for drug safety assessment is still a major challenge.…”

Section: Cardiotoxicity Of Small Molecules: Drug Screening Using the mentioning

confidence: 99%

“…Although simpler than humans, zebrafish are also complex vertebrates that maintain equally elaborate mechanisms to activate or relieve the effects of exogenous chemicals [81] . Thus, the close resemblance of the genetic cascade governing heart development in zebrafish to that of humans has propelled the zebrafish system as a cost-effective model to conduct pharmacological screens on developing embryos and larvae as well as to provide data to generate computational models to evaluate in silico drugs studies [79,81] .…”

Section: Cardiotoxicity Of Small Molecules: Drug Screening Using the mentioning

confidence: 99%

See 3 more Smart Citations

Zebrafish as Toxicological model for screening and recapitulate human diseases

Caballero¹,

Candiracci²

2018

JUMD

View full text Add to dashboard Cite

Embryonic and larval Danio rerio (zebrafish) is increasingly used as a toxicological model to conduct rapid in vivo tests and developmental toxicity assays; the zebrafish features high genetic homology to mammals, robust, phenotypes, highthroughput genetic and chemical screening have made it a powerful tool to evaluate in vivo toxicity. New methodologies of genome editing as CRISPR/Cas9; ZFN and TALEN make it a suitable model to perform studies to pair human genetic diseases as well. This review surveys recent studies employing zebrafish as experimental model, comparing it with other in vivo and in vitro models, presenting zebrafish as a potent vertebrate tool to evaluate drug toxicity and efficacy in order to facilitate more extensive, easy and comprehensive knowledge of new generation drugs.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Cardiotoxicity Of Small Molecules: Drug Screening Using the mentioning

confidence: 99%

Section: Cardiotoxicity Of Small Molecules: Drug Screening Using the mentioning

confidence: 99%

Section: Cardiotoxicity Of Small Molecules: Drug Screening Using the mentioning

confidence: 99%

See 2 more Smart Citations

Zebrafish as Toxicological model for screening and recapitulate human diseases

Caballero¹,

Candiracci²

2018

JUMD

View full text Add to dashboard Cite

show abstract

“…One possible approach is to design the trial using a Bayesian approach, and to treat the predictions from the virtual patients as an a priori probability. 48 A fourth somehow related use case refers to situations where the de-risking with conventional clinical trials is impossible, or unsustainable. Osteogenesis imperfecta (OI) has a prevalence of 1/20,000 new born, which makes roughly 200 children per year in the USA.…”

Section: In Silico Clinical Trials: Use Cases Current and Futurementioning

confidence: 99%

In silico clinical trials: how computer simulation will transform the biomedical industry

2016

View full text Add to dashboard Cite

<p class="abstract">The term ‘in silico clinical trials indicates the use of individualised computer simulation in the development or regulatory evaluation of a medicinal product, medical device, or medical intervention. This review article summarises the research and technological roadmap developed by the Avicenna Support Action during an 18 month consensus process that involved 577 international experts from academia, the biomedical industry, the simulation industry, the regulatory world, etc. The roadmap documents early examples of in silico clinical trials, identifies relevant use cases for in silico clinical trial technologies over the entire development and assessment cycle for both pharmaceuticals and medical devices, identifies open challenges and barriers to a wider adoption and puts forward 36 recommendations for all relevant stakeholders to consider<span lang="EN-US">.</span></p>

show abstract

Zebrafish: An emerging model system to study liver diseases and related drug discovery

Katoch

Patial

2020

J of Applied Toxicology

View full text Add to dashboard Cite

The zebrafish has emerged as a powerful vertebrate model for studying liverassociated disorders. Liver damage is a crucial problem in the process of drug development and zebrafish have proven to be an important tool for the highthroughput screening of drugs for hepatotoxicity. Although the structure of the zebrafish liver differs to that of mammals, the fundamental physiologic processes, genetic mutations and manifestations of pathogenic responses to environmental insults exhibit much similarity. The larval transparency of the zebrafish is a great advantage for real-time imaging in hepatic studies. The zebrafish has a broad spectrum of cytochrome P450 enzymes, which enable the biotransformation of drugs via similar pathways as mammals, including oxidation, reduction and hydrolysis reactions. In the present review, we appraise the various drugs, chemicals and toxins used to study liver toxicity in zebrafish and their similarities to the rodent models for liverrelated studies. Interestingly, the zebrafish has also been effectively used to study the pathophysiology of nonalcoholic and alcoholic fatty liver disease. The genetic models of liver disorders and their easy manipulation provide great opportunity in the area of drug development. The zebrafish has proven to be an influential model for the hepatic system due to its invertebrate-like advantages coupled with its vertebrate biology. The present review highlights the pivotal role of zebrafish in bridging the gap between cell-based and mammalian models.

show abstract

The virtual heart as a platform for screening drug cardiotoxicity

Cited by 39 publications

References 97 publications

Zebrafish as Toxicological model for screening and recapitulate human diseases

Zebrafish as Toxicological model for screening and recapitulate human diseases

In silico clinical trials: how computer simulation will transform the biomedical industry

Zebrafish: An emerging model system to study liver diseases and related drug discovery

Contact Info

Product

Resources

About