Complexity of Molecular Genetics in the Inherited Cardiac Arrhythmias

Lahrouchi, Najim; Wilde, Arthur A.M.

doi:10.1016/b978-0-12-802002-9.00014-5

Cited by 1 publication

(3 citation statements)

References 143 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, antiarrhythmic agents are known to cause pro-arrhythmia. [ 13 14 ] The cell line-based assays to detect organ-specific toxicity are used; however, in vivo biology cannot be mimicked and toxicity cannot be estimated at the optimal level. Initially, zebrafish have been used for toxicity studies of environmental pollutants, agrochemical compounds; however, in the last 20 years, the pharmaceutical industry witnessed increasing use of zebrafish whole-organism screening model for toxicity studies.…”

Section: Toxicity Studies In Zebrafishmentioning

confidence: 99%

“…Phase 3 is followed by Phase 4, the resting phase, in which only potassium channels remain open and due to potassium efflux, there is an establishment of negative resting membrane potential. [ 13 ] The QT interval represents the time between ventricular depolarization and repolarization. The ST segment is the start of ventricular repolarization.…”

Section: Cardiotoxicitymentioning

confidence: 99%

“…ST-segment elevation may indicate myocardial infarction. [ 13 14 20 21 22 ] As enlisted in Table 4 , numbers of drugs are screened for cardiotoxicity in zebrafish embryos model. [ 23 24 25 ] There is a high concordance in results obtained with cardiotoxic and noncardiotoxic drugs tested in humans and zebrafish.…”

Section: Cardiotoxicitymentioning

confidence: 99%

See 2 more Smart Citations

Zebrafish: An emerging whole-organism screening tool in safety pharmacology

et al. 2020

View full text Add to dashboard Cite

During the last two decades, the development in drug discovery is slackening due to drug withdrawal from the market or reported to have postmarket safety events. The vital organ toxicities, especially cardiotoxicity, hepatotoxicity, pulmonary toxicity, and neurotoxicity are the major concerns for high drug attrition rates. The pharmaceutical industry is looking for high throughput, high content analysis based novel assays that would be fast, efficient, reproducible, and cost-effective; would address toxicity, the safety of lead molecules, and complement currently used cell-based assays in preclinical testing. The use of zebrafish, a vertebrate screening model, for preclinical testing is increasing owing to the number of advantages and striking similarities with the mammal. The zebrafish embryo development is fast and all vital organs such as the heart, liver, brain, pancreas, and kidneys in zebrafish are functional within 96–120hpf. The maintenance cost of zebrafish is reasonably low as compared to mammalian systems. Due to these features, zebrafish has arisen as a potential experimental screening model in lead identification and validation in the drug efficacy, toxicity, and safety evaluation. Numbers of drugs and chemicals are screened using zebrafish embryos, and results were found to show 100% concordance with mammalian screening data. The application of zebrafish, being a whole-organism screening model, would show a significant reduction in the cost and time required in the drug development process. The present challenge includes complete automation of the zebrafish screening model, i.e., from sorting, imaging of embryos to data analysis to accelerate the therapeutic target identification, and validation process.

show abstract

Section: Toxicity Studies In Zebrafishmentioning

confidence: 99%

Section: Cardiotoxicitymentioning

confidence: 99%