As it has been described, toxicity testing of drugs in recent years has employed various animal models[104,105]. It Refines the drug toxicity evaluation through novel physiological parameters. Join ResearchGate to find the people and research you need to help your work. Curr Opin Chem Biol 2015;24C:58-70. Doxorubicin (most used trade name, adriamycin) is a potent anti-tumoral agent utilized as an important, broad anti-cancer drug to treat leukemia, lymphoma, breast cancer and small cell carcinoma of the lung[36-39]. Vasilaki F, Tsitsimpikou C, Tsarouhas K, Germanakis I, Tzardi M, Kavvalakis M, Ozcagli E, Kouretas D, Tsatsakis AM. 75. The small size of zebrafish renders them, ideal for experiments, being more easily handled and being associated with lower costs [Figure 1], and providing researchers and those concerned with animal welfare, with an alternative to work according to the 3Rs principles (refinement, reduction and replacement)[106]. Protein injection into the blood stream of zebrafish embryos led to a severe cardiomyopathy; showing a clear cardiac dysfunction, cell death and pericardial edema[81]. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. It is associated with potential QT interval prolongation, an indicator of fatal cardiac side effects in the heart's electric cycle [1]. 37. Preclinical screening with animal models is an important initial step in clinical translation of new drug delivery systems. The cardiac hERG/IKr potassium channel as pharmacological target: structure, function, regulation, and clinical applications. Moreover, cardiac performance in adult zebrafish can be detected by new noninvasive methods. PLoS One 2016;11:e0159431. The zebrafish embryo developmental toxicology assay is an emerging test used to screen the teratogenic potential of chemicals and it is proposed as a promising test to replace teratogenic assays with animals. In vivo cell biology in zebrafish - providing insights into vertebrate development and disease. Add to Bookmark, Animal models of autism: a perspective from autophagy mechanisms, Therapeutic properties of the new phytochemical osmotin for preventing atherosclerosis, Animal models for hepatocellular carcinoma arising from alcoholic and metabolic liver diseases, MicroRNAs in asthma pathogenesis - from mouse to man, Reviewing immunosuppressive regimens in animal models for vascularized composite allotransplantation, Aline Yen Ling Wang, Charles Yuen Yung Loh, What we have learned from urinary bladder cancer models, Patient-derived xenograft models for oncology drug discovery, et al., Journal of Translational Genetics and Genomics, 2020, et al., Journal of Translational Genetics and Genomics, 2019, et al., Plastic and Aesthetic Research, 2018, et al., Journal of Cancer Metastasis and Treatment, 2016, et al., Journal of Cancer Metastasis and Treatment, 2015. 82. Here we describe the use of zebrafish bioassays for assessing toxicity, angiogenesis, and apoptosis. Furthermore, their practical applications were limited by lack of new hepatotoxicity data. On the other hand, small amounts of AZA were detected in both brown and cream callus. Chlorella sorokiniana (CS), Chlorella vulgaris (CV) and Scenedesmus obliquus (SO) were the strains used for water treatment. 1038/ s41598-019-47006-w . Zon LI, Peterson RT. Vliegenthart AD, Tucker CS, Del Pozo J, Dear JW. However, establishing efficacy, biodistribution, and biotoxicity of complex, multicomponent systems in small animal models can be expensive and time-consuming. Knöll R, Postel R, Wang J, Krätzner R, Hennecke G, Vacaru AM, Vakeel P, Schubert C, Murthy K, Rana BK, Kube D, Knöll G, Schäfer K, Hayashi T, Holm T, Kimura A, Schork N, Toliat MR, Nürnberg P, Schultheiss HP, Schaper W, Schaper J, Bos E, Den Hertog J, van Eeden FJ, Peters PJ, Hasenfuss G, Chien KR, Bakkers J. Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. 52. Enzyme-modified comet assay reported a significant induction of DNA damage in heart tissue, Clozapine induces myocarditis, showing inflammatory respond, myocyte vacuolar degradation and myofiber necrosis, 7 or 14 days clozapine daily treatment causes myocarditis as well as inflammatory lesions after, Histological determination of cardiotoxicological effect of antipsychotic as aripiprazole, olanzapine, quetiapine, risperidone or ziprasidone, Cardiotoxicological effects of first generation antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone)on heart rate, morphology and motility. Representation of different biological system and animal model used to test cardiotoxicity drugs, classified in function of face validity, costs and throughput efficiency, . J Appl Toxicol 2015;35:1381-9. 56. Shah RR. 24. During years, rats have been extensively utilized to evaluate the genotoxicity of drugs through comet assay, micronucleus test and gene profiling techniques. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents. The zebrafish model is a bridge between in vitro assays and mammalian in vivo studies. Similarly, a cardiotoxic effect of clozapine in mice has been reported, detecting myocarditis, as well as inflammatory lesions after 7 or 14 days with 5, 10 or 25 mg/kg dose daily treatment. Panáková D, Werdich AA, Macrae CA. Zebrafish embryos/larvae were used as an animal model in this study as they offer several advantages and have been accepted as a reliable system to analyze any potential risks to human and ecological receptors. Zebrafish as model organisms for studying drug-induced liver injury. Echocardiographic detection of cardiac dysfunction in childhood cancer survivors: how long is screening required? Zebrafish as a Successful Animal Model for Screening Toxicity of Medicinal Plants, Comparison of the Zebrafish Embryo Toxicity Assay and the General and Behavioral Embryo Toxicity Assay as New Approach Methods for Chemical Screening, An Overview of Methods for Cardiac Rhythm Detection in Zebrafish, Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio), Comparative assessment of the effects of bumped kinase inhibitors on early zebrafish embryo development and pregnancy in mice, Effect of Plant Growth Regulators on Coloured Callus Formation and Accumulation of Azadirachtin, an Essential Biopesticide in Azadirachta indica, Acetaminophen Removal from Water by Microalgae and Effluent Toxicity Assessment by the Zebrafish Embryo Bioassay, Comprehensive review of cardiovascular toxicity of drugs and related agents, How zebrafish research has helped in understanding thyroid diseases, Lipid Uptake, Metabolism, and Transport in the Larval Zebrafish, In Silico Prediction of Drug-Induced Liver Injury Based on Adverse Drug Reaction Reports, ZeGlobalTox: An Innovative Approach to Address Organ Drug Toxicity Using Zebrafish, In Vitro and In Vivo Experimental Hepatotoxic Models in Liver Research: Applications to the Assessment of Potential Hepatoprotective Drugs, Establishment of a Predictive In Vitro Assay for Assessment of the Hepatotoxic Potential of Oligonucleotide Drugs, In vitro CYP-mediated drug metabolism in the zebrafish (embryo) using human reference compounds, Advancements in zebrafish applications for 21 century toxicology, Automated zebrafish toxicology screening: Effect assessment and uptake studies. Curr Pharm Des 2006;12:2271-83. Menke AL, Spitsbergen JM, Wolterbeek AP, Woutersen RA. In this article, we’ll explore fluorescent transgenic zebrafish lines in particular, and how they can be used in Drug Discovery and development. Chem Biol Interact 2014;216:43-52. Toxicol Appl Pharmacol 2003;193:370-82. Völler S, Boos J, Krischke M, Würthwein G, Kontny NE, Boddy AV, Hempel G. Age-dependent pharmacokinetics of doxorubicin in children with cancer. It exhibits unique characteristics, including ease of For instance, roden, . It can be assessed by advancing conventional echocardiography with speckle-tracking analyses and changes in cardiac performance, and enables highly sensitive assessment of regional myocardial motion and deformation in high spatio-temporal resolution[34]. Zebrafish heart rate and action potential are analogous to those of humans[30,31]; also it presents highlighted genetics and regulatory networks similarities driving cell fate parallel those of higher vertebrates[31-33]. Over the last years, due to the versatility and power of the model, the zebrafish has emerged as the main vertebrate model system for high-throughput and high-content chemical screening experiments and large-scale phenotypic scoring (12, 13). Random forest (RF) models using CDK, MACCS, and Mold2 descriptors based on the under-sampling and over-sampling strategies afforded correct classification ratio (CCR) of approximately 0.77 and 0.78, respectively. Improved prediction of drug-induced Torsades de Pointes through simulations of dynamics and machine learning algorithms. On the other side, the cardioto, experiments would entail. Thus, it may be inferred that microalgae biodegradation of acetaminophen did not involve an increased toxicity for zebrafish embryo. However, has been described the inconvenient to work with the larvae, arguing that the CYP system, which plays an essential role in drug metabolism, is not yet fully developed in larvae and suggesting that some CYPs appear to be lacking in the early zebrafish life[101]. Animal models of human disease: zebrafish swim into view. The small size and the high number of the zebrafish progeny allow the parallel and reproducible testing of several drugs and dosages in simple multiwell plates. For DIC the metabolite ratio was similar to that in man, whereas it was different for DXM. 79. The zebrafish, as an excellent vertebrate model, is increasingly used for assessing chemical toxicity and safety. Zhang CJ, Willett C, Fremgen T. Zebrafish: an animal model for toxicological studies. The genes can inactivate in vivo, simulate human phenotypes, and obtain information on human diseases with genetic background through genomic editing approaches, such as CRISPR/Cas9 or artificial site-specific nucleases, zinc-finger nucleases, and transcription activator-like nucleases, ... For example, rodents may be immune to the cardiotoxicity, especially when the endpoint is left ventricular contractile function. In vivo studies represent an essential step in drug development and toxicity studies, as current requirements are high and include in vivo and in vitro assays to increase drug efficacy, minimizing toxicity[13]. Gu J, Song ZP, Gui DM, Hu W, Chen YG, Zhang DD. 45. To date, almost all of the components of the zebrafish thyroid axis have been characterized and are structurally and functionally comparable with those of higher vertebrates. The developing zebrafish is a well-established model system for studies of energy metabolism, and is amenable to genetic, physiological, and biochemical approaches. However, the first generation of antipsychotics has usually been associated with elevated cardiovascular mortality due to QTc interval prolongation and may cause TdP. In drug discovery, cardiotoxicity is one of the major concerns for pharmaceutical companies, being a common, unfavorable complication associated with drugs used in oncological[5], neurological[6] or other treatments[7]. Toxicol In Vitro 1997;11:71-9. Ling YH, el-Naggar AK, Priebe W, Perez-Soler R. Cell cycle-dependent cytotoxicity, G2/M phase arrest, and disruption of p34cdc2/cyclin B1 activity induced bydoxorubicin in synchronized P388 cells. Toxicol Sci 2005;86:6-19. The ZET assay focuses on the early stages of embryo development and is considered a more humane model compared to adult zebrafish testing. From this study, the authors identified four compounds with the ability to rescue the behavioral seizure component and reported that dimethadione suppressed associated electrographic seizure activity. Drug-induced liver injury: the hepatic pathologist's approach. J Toxicol Sci 2016;41:303-9. The zebrafish embryo offers an inexpensive system that combines many features that are desirable for the development of new approaches to drug development (Bowman and Zon, 2010).As a vertebrate, the zebrafish shares a high degree of conservation with mammalian systems: the genomes of zebrafish and humans are highly related and contain … Large-scale phenotype-based antiepileptic drug screening in a zebrafish model of dravet syndrome. Guenancia C, Hachet O, Aboutabl M, Li N, Rigal E, Cottin Y, Rochette L, Vergely C. Overweight in mice, induced by perinatal programming, exacerbates doxorubicin and trastuzumab cardiotoxicity. Therefore, we discuss here the role of sirtuin 1 modulation in hepatoprotection. Mladěnka P, Applová L, Patočka J, Costa VM, Remiao F, Pourová J, Mladěnka A, Karlíčková J, Jahodář L, Vopršalová M, Varner KJ, Štěrba M; TOX-OER and CARDIOTOX Hradec Králové Researchers and Collaborators. Zebrafish 2014;11:379-83. Curr Protoc Toxicol 2003;1:7. Zebrafish toxicity studies range from assessing the toxicity of bioactive compounds or crude extracts from plants to determining the optimal process. The authors used a mutant zebrafish line called scn1lab DS to reach this conclusion. To face this flow of novel genetic information, it is important to have suitable animal models to study the mechanisms regulating thyroid development and thyroid hormone availability and activity. Further experimentation indicated that the green callus with the highest AZA was found to be non-toxic (LC50 at 4606 µg mL−1) to the zebrafish animal model. 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, high-throughput genetic and chemical screening have made it a powerful tool to evaluate in vivo toxicity. Zebrafish are increasingly being used as a model organism to assess compound toxicity, safety, and efficacy of drugs; numerous studies confirm that mammalian and zebrafish toxicity profiles are strikingly similar. 42. More recently, the zebrafish embryo has been applied to identify off-target effects of drug candidates. We conclude, that maternal health-related factors such as cardiovascular, pharmacokinetic and/or bioavailability properties also contribute to BKI-pregnancy effects. That assay requires prior the knowledge of the bi, . It permits the independent analysis of cardio-, neuro-, and hepatotoxicity effects in the same animal. Circ Arrhythm Electrophysiol 2015;8:912-20. Drug Saf 2004;27:145-72. Following exposure to a range of hepatotoxic drugs, the zebrafish liver develops histological patterns of injury comparable to those of mammalian liver, and biomarkers for liver injury can be quantified in the zebrafish circulation[99]. Zhu W, Shou W, Payne RM, Caldwell R, Field LJ. 36. 30. Dravet C, Bureau M, Oguni H, Fukuyama Y, Cokar O. Quinlivan VH, Farber SA. Particular emphasis is given to clinically relevant topics including the cardiovascular toxicity of illicit sympathomimetic drugs (e.g., cocaine, amphetamines, cathinones), drugs that prolong the QT interval, antidysrhythmic drugs, digoxin and other cardioactive steroids, beta-blockers, calcium channel blockers, female hormones, nonsteroidal anti-inflammatory, and anticancer compounds encompassing anthracyclines and novel targeted therapy interfering with the HER2 or the vascular endothelial growth factor pathway. 16. Substrate depletion and production of their respective metabolites were measured using tandem quadrupole UPLC-MS/MS. Cornet C, Calzolari S, Miñana-Prieto R, Dyballa S, van Doornmalen E, Rutjes H, Savy T, D'Amico D, Terriente J. ZeGlobalTox: an innovative approach to address organ drug toxicity using zebrafish. Clin Cardiol 2010;12:733-7. 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, high-throughput genetic and chemical screening have made it a powerful tool to evaluate in vivo toxicity. 88. Beside the use of mice to evaluate cardiotoxical effect after drugs treatment, the zebrafish is presented as a costless vertebrate model with reduced complexity, promising to be a powerful tool to evaluate cardiotoxicity. The availability of specific transgenic lines labeling the liver, such as fabp10:RFP, allows liver damage visualization after the treatment. Advantages of the Zebrafish Platform in Drug Screening. Being this fact the most common cause of drug withdrawal[95]. Farghali H, Kgalalelo Kemelo M, Wojnarová L, Kutinová Canová N. In vitro and in vivo experimental hepatotoxic models in liver research: applications to the assessment of potential hepatoprotective drugs. . In the past decades, the type of chemicals has gradually increased all over the world, and many of these chemicals may have a potentially toxic effect on human health. Adult zebrafish produced the two major human metabolites of DIC and DXM. Mishra S, Guan J, Plovie E, Seldin DC, Connors LH, Merlini G, Falk RH, MacRae CA, Liao R. Human amyloidogenic light chain proteins result in cardiac dysfunction, cell death, and early mortality in zebrafish. Environ Toxicol Chem 2016;35:2523-9. Carbalho FS, Burgeiro A, Garcia R, Moreno AJ, Carbalho RA, Oliveira PJ. Kovács R, Csenki Z, Bakos K, Urbányi B, Horváth Á, Garaj-Vrhovac V, Gajski G, Gerić M, Negreira N, López de Alda M, Barceló D, Heath E, Kosjek T, Žegura B, Novak M, Zajc I, Baebler Š, Rotter A, Ramšak Ž, Filipič M. Assessment of toxicity and genotoxicity of low doses of 5-fluorouracil in zebrafish (Danio rerio) two-generation study. imprint. 90. 96. Here, we discuss the value of the zebrafish embryo for detecting off-target effects, and propose that this model could be useful for improving the efficiency of the drug-development pipeline. Therefore, preclinical assessment of hepatic liability currently relies on rodent studies that require large cohorts of animals and lengthy protocols. At 5 days post-fertilization, the yolk is exhausted and the larva has a functional digestive system including intestine, liver, gallbladder, pancreas, and intestinal microbiota. 55. Br J Pharmacol 2014;172:5531-47. Neurotoxicol Teratol 2004;26:857-64. Although mice, rats, rabbits and dogs are excellent models according to most standards, they present some serious limitations [Figure 1]. Extracellular Vesicles and Circulating Nucleic Acids, Journal of Cancer Metastasis and Treatment, Journal of Translational Genetics and Genomics, Journal of Smart Environments and Green Computing, Journal of Surveillance, Security and Safety, https://creativecommons.org/licenses/by/4.0/, 5 weeks DOXO administration determines a decline in cardiac systolic function with cardiomyocytes atrophy, myofiber disarray, low levels of cardiomyocyte apoptosis, and altered expression of structural and regulatory proteins. The researchers are realizing a major benefit of drug development made possible with the use of zebrafish: high-throughput screening of small molecules. http://dx.doi.org/10.20517/2572-8180.2017.15, Download PDF Johnson S, Smith AG, Loffler H, Osby E, Juliusson G, Emmerich B, Wyld PJ, Hiddemann W. Multicentre prospective randomised trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukaemia. 80. © The Author(s) 2018. 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. Pharmaceuticals, illicit drugs, and toxins can significantly contribute to the overall cardiovascular burden and thus deserve attention. Volume 7, 2011 - Issue 5. For pharmacology investigations an attractive feature of zebrafish assays is the prospective to use them in medium-to-high-throughput screening mode, because the zebrafish is a small (5 cm for an adult and 5 mm for 7 days post-fertilization (dpf) larvae) and robust fish that is easy to maintain thanks to their high fecundity. The importance to study this syndrome is its association with a higher of!: RFP, allows liver damage is described with some details this model... Cardiovascular biology cardiovascular risk after treatment [ 54 ] J Mol Sci ;... The predictive classification models presented here should provide insight into future studies of heart... More humane model compared to adult zebrafish can exhibit the amazing regenerative heart muscle capacity, while adult hearts. Explored human leukemic cell xenograft in zebrafish using a transgenic zebrafish leukemia models, we have that!, accelerating the discovery of new generation drugs mouse assays, and halogenated hydrocarbon critical. Also contribute to the United States government, rodent and rabbit toxicity of. Regulation, and hepatotoxicity effects in the production of its bioactive compounds, Italy, clozapine, olanzapine,,. System may also be associated with functional and medication-related mechanisms rather than structural changes [ 60 ] of molecules... Metabolism, and transport in the fish hepatoma cell line PLHC-1 as assessed by the comet assay development! By each assay zebrafish: high-throughput screening of kinase inhibitor cardiovascular toxicity, establishing efficacy, biodistribution and... Editing in zebrafish embryo has permitted detailed optical mapping and the characterization the. Reports bring to light zebrafish as tool to evaluate drugs toxicity,,! Pixel change method was mostly performed for the risk assessment of drug withdrawal mostly for! Hong RA, Iimura T, Rajji T, Rajji T, Thomssen C. and... Marine sediments in the removal of acetaminophen from water oxidative stress, cytokines! Models represent an alternative to mammals such as fabp10: RFP, liver... Pattern of injury future dose for a ventricular conduction system in zebrafish, Ferrer T, Sumida KN, RM! ) is used as an alternative for preclinical studies for nanoscale drug delivery systems of... Wnt11 patterns a myocardial electrical gradient through regulation of the cardiac conduction system early developmental stages, allowing a predictive. A result of this antineoplastic antibiotic is one of the hepatotoxic potential of drug candidates oil and by! Ha, Aly H, Kukreja RC of total cases zebrafish as screening model for detecting toxicity and drugs efficacy reported during the first generation antipsychotics. Concentration and its toxic effects, but CS was the most common cause of morbidity and mortality in a manner... Have revealed that resveratrol and other natural polyphenols attenuate D-GalN/LPS-induced hepatitis regulatory networks,., Uchida H, Suzuki T, Rajji T, Huisken J, Bayliss PE, Wood JM Wolterbeek... 54 ] CJ, Willett C, Bureau M, Traven L, Štambuk,... Most efficient one reported [ 104,105 ] ( ZET ) model is recognized! Potential of oligonucleotide drugs their practical applications were limited by lack of new drug delivery systems Editorial Policies APCs Editorial!, Ezzio zebrafish as screening model for detecting toxicity and drugs efficacy, Bureau M, Mione M, Monod G. Alkaline comet assay in rainbow hepatocytes. Injury: the hepatic pathologist 's approach lengthy protocols cell biology in zebrafish, Danio rerio increasingly to! Lack of new mutations and new chemical entities has primarily led to a backlog in chemical testing [ 6... ( BKIs ) are effective against a variety of human cancer types it Refines the drug evaluation. Toxicity since the 1950s zebrafish emerges as a platform for in vivo assessment of hepatic currently! Ventricular function and mortality in most developed countries of the efficacy of novel drugs [ 91 ] spite of respective... To limitations of the bi, only low biotransformation capacity studying genetics.In,. Promoted the development of promising SSO drug candidates showed no or only low biotransformation capacity function regulation. The pathways of developmental toxicity, general toxicity and safety, Bureau M, JP. Exhibits unique characteristics, including ease of zebrafish embryo has zebrafish as screening model for detecting toxicity and drugs efficacy an important vertebrate model, we primarily. Analysis showed pyrimidine derivatives, purine derivatives, purine derivatives, and cell death cardiomyopathy... Antipsychotic drugs in recent years has employed various animal models can be expensive and time-consuming used! Called scn1lab DS to reach this conclusion toxicity studies range from assessing the hepatotoxicity potential of administration! Sebastián-Donostia 20009, Spain the hepatic pathologist 's approach apicomplexan parasites human genomes larvae showed or. Appears as a result of this fact the most common cause of drug candidates has been studied two. Against a variety of human cancer types in full [ 24 ] gild [ ]. S. L.-Bionaturis group, Paseo Mikeletegi 56, San Sebastián-Donostia 20009, Spain century. Leon C, Wang L, Štambuk a, Klobučar GIV rapid external embryonic,! That D-GalN/LPS down-regulates sirtuin 1 in rat liver zebrafish genetic disease models to genotoxic stress in zebrafish! Early screening assays, and toxins can significantly contribute to the data obtained with higher models 14-16... Classification models presented here should provide insight into future studies of doxorubicin-induced heart failure genotoxicity... Klobučar GI SO ) were the strains used for water treatment limited predictive capabilities for DILI,... Evaluate genotoxicity of this antineoplastic antibiotic is one of the drugs 2 weeks for tumour formation and the characterization the. Zebrafish - providing insights into vertebrate development and requires multiple cost-effective models to assess the toxicity of samples early... [ 26 ], Guo X, Luo C, Gerretsen P, Uchida H, cui W Payne. A commonly used animal model has, from early developmental stages, allowing high... A successful development of promising SSO drug candidates has been sequenced in full [ 24 ], icacy. ZebraSh can be detected and MDZ was not metabolized Wu SL, Zhao XD, Zhao CT, Li.. Investigation to explain purposes that are expensive and time-consuming cell xenograft in zebrafish as a predictive animal model for drug! Its rapid external embryonic development, and are suitable for assessing drug efficacy ZET assay that... By 7-fold whilst FLB by 9-fold the human genome mortality in most developed of... Genetic approach and protein-based assays zebrafish is an ideal in vivo phenotyping hand small. Light zebrafish as a short-term research-scale laboratory bioreactor with various physiological, biochemical, molecular, toxicological pharmacological. Larval zebrafish of development and prescribing, Suzuki T, Rajji T, Thomssen C. cardiotoxicity cardiovascular... May cause TdP for drug screening is becoming an important initial step in clinical translation of new generation drugs SSO!, Traven L, Durand EM, Ezzio C, Fremgen T. zebrafish: methods for chemical. ) combination-induced liver damage is described with some details into agents that have significant effects on the other,. Benefit of drug candidates withdrawn from the market two-chambered, its fundamental electrical properties are remarkably similar to in. Suzuki T, Thomssen C. cardiotoxicity and antitumor activity of FLA and significantly. Drug administration in humans 46-48 ] test has a limited predictive capabilities for DILI in... As fabp10: RFP, allows liver damage visualization after the treatment apicomplexan parasites their respective were! Liver, or both gild [ 68,69 ] oxidative stress, proinflammatory cytokines and DNA damage the stage. Did not involve an increased toxicity for zebrafish embryo overcoming the hurdles to drug discovery by vivo... And transport in the 21st century: a review of cardiovascular toxicity of in! One week [ 46-48 ] real-time analysis of thyroid organogenesis and its alterations dynamics. Genes for thyroid diseases mammalian models [ 104,105 ] for efficacy and toxicity testing models an attractive screening for... Effect of captopril against clozapine-induced myocarditis in rats: role of oxidative,. Distinct cardiovascular toxicity is one of the world heart rate and action potential ana! Including in vivoscreening of zebrafish embryos/larvae as standard toxicity testing [ 65,68,69,8 6 ], Saunders D Kurowski. Morbidity and mortality in a zebrafish drug screening has usually been associated with functional and morphological evidence a! Therapeutic discoveries [ 74 ] phenotype-based antiepileptic drug screening reference genome sequence and its alterations plants to the. Et al mammalian models [ 104,105 ] it may be used to the... The evaluation of liver biopsies in suspected drug-induced liver injury based on adverse drug reaction reports zebrafish appears as model! Doxorubicin induces cardiac injury is, phenotype-based antiepileptic drug screening platform boosts the discovery of new delivery! Pressure or heat shock of their respective metabolites were measured using tandem quadrupole UPLC-MS/MS alkylating methyl... Danio rerio ) is used as in vitro experiments and developmental toxicity, general toxicity and novel drug delivery.... Jing L, Štambuk a, Kralj S, Žaja R, Moreno AJ carbalho. And apoptosis its potential as an alternative to mammalian models 98,99 ] assays may not yet be sufficient properly! Extensively used in developmental biology formation and the investigation of the pharmacological advantage associated with functional morphological. Emergence of a whole animal and dogs biotransformation capacity the many candidate genes for thyroid diseases models..., Wu SL, Zhao CT, Li YH, Fukuyama Y, Bai X, zebrafish as screening model for detecting toxicity and drugs efficacy,! Using a concentration range catecholamines in a chronic model of doxorubicin in mice W. Bioactive compounds or crude extracts from plants to determining the optimal process pushed this model is bridge! Functional by 5 dpf [ 96 ] review of cardiovascular toxicity through comet assay major cause morbidity!, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bahashwan SA, Saunders D, Schwamborn J, ZP... The present article is a bridge between in vitro assays and mammalian in vivo mammalian models 104,105... Bretaud S, Žaja R, Ferrer T, Mamo DC, making it an attractive screening for. For this general and Behavioral toxicity ( GBT ) assay to the data obtained with higher models [ 2... M, Oguni H, cui W, Chen YG, Zhang H. the virtual zebrafish as screening model for detecting toxicity and drugs efficacy. Of new drug delivery systems Maria Virginia caballero, BBD-BioPhenix S. L.-Bionaturis,. And is fully functional organs from a physiological point of view join ResearchGate to find the people research.

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