Zebrafish Xenotransplant Cancer Model for Drug Screening

Li, Chunqi; Luo, Laihui; McGrath, Patricia

doi:10.1002/9781118102138.ch17

Cited by 6 publications

(7 citation statements)

References 22 publications

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“…23,[29][30][31][32] We use zebrafish because of their many advantages such as short generation times, amenability for large-scale screening, high fecundity, ease of in vitro fertilization, and transparency. 4,33,34 Other important advantages of the zebrafish as an animal model are that the morphological and molecular basis of tissues and organs is either identical or similar to other vertebrates, including humans. 23,35 Research regarding the zebrafish hematological system shows that human platelets and coagulation factors share many characteristics with their zebrafish counterparts.…”

Section: Discussionmentioning

confidence: 99%

A Zebrafish Thrombosis Model for Assessing Antithrombotic Drugs

Zhu

Liu²,

Guo³

et al. 2016

Zebrafish

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Thrombosis is a leading cause of death and the development of effective and safe therapeutic agents for thrombotic diseases has been proven challenging. In this study, taking advantage of the transparency of larval zebrafish, we developed a larval zebrafish thrombosis model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days post fertilization) were treated with phenylhydrazine (PHZ) and a testing drug for 24 h. Tested drugs were administered into the zebrafish either by direct soaking or circulation microinjection. Antithrombotic efficacy was quantitatively evaluated based on our previously patented technology characterized as an image analysis of the heart red blood cells stained with O-dianisidine staining. Zebrafish at 2 dpf treated with PHZ at a concentration of 1.5 μM for a time period of 24 h were determined as the optimum conditions for the zebrafish thrombosis model development. Induced thrombosis in zebrafish was visually confirmed under a dissecting stereomicroscope and quantified by the image assay. All 6 human antithrombotic drugs (aspirin, clopidogrel, diltiazem hydrochloride injection, xuanshuantong injection, salvianolate injection, and astragalus injection) showed significant preventive and therapeutic effects on zebrafish thrombosis (p < 0.05, p < 0.01, & p < 0.001) in this zebrafish thrombosis model. The larval zebrafish thrombosis model developed and validated in this study could be used for in vivo thrombosis studies and for rapid screening and efficacy assessment of antithrombotic drugs.

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Section: Discussionmentioning

confidence: 99%

A Zebrafish Thrombosis Model for Assessing Antithrombotic Drugs

Zhu

Liu²,

Guo³

et al. 2016

Zebrafish

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“…Total fluorescent signal (S) = area of ROI × average fluorescent intensity in ROI. Drug effect on zebrafish GI motility was quantified based on the total fluorescent signal in zebrafish GI tract . Effect of a test drug or compound on GI motility was calculated using the formula below:

Drug effect on GI emptying false(% false) = (1 - \frac{normalS false(compound false)}{normalS false(vehicle false)}) \times 100 %

…”

Section: Methodsmentioning

confidence: 99%

“…Zebrafish Danio rerio is emerging as a predictive vertebrate animal model for in vivo assessment of drug efficacy, toxicity, and safety. [10][11][12][13][14] An important advantage of the zebrafish animal model is that the morphological and molecular basis of tissues and organs is either identical or similar to other vertebrates, including humans. 15,16 The sequence and presumed function of many genes that are important for vertebrates are conserved in the zebrafish.…”

Section: Introductionmentioning

confidence: 99%

Human prokinetic drugs promote gastrointestinal motility in zebrafish

Zhou

Guo²,

Zhang³

et al. 2014

Neurogastroenterology Motil

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“…Zebrafish, Danio rerio, is emerging as a predictive vertebrate animal model for in vivo assessing toxicity, safety and efficacy of compounds and drugs and numerous studies have confirmed that mammalian and zebrafish toxicity profiles are strikingly similar (McGrath and Li, 2008). In earlier investigations, we and others have developed a variety of zebrafish assays and disease models for drug toxicity and metabolism assessment and for cancer drug screening (D' Amico et al, 2012;Li et al, 2012aLi et al, , 2012bMcGrath and Li, 2008). As a vertebrate animal, zebrafish and humans have approximately 85% homology in genomes (Milan et al, 2006) and their morphological and molecular basis of tissue and organ development is either identical or similar to other vertebrates including humans (Chen and Fishman, 1996;Granato and Nüsslein-Volhard, 1996).…”

Section: Introductionmentioning

confidence: 99%

Human cardiotoxic drugs delivered by soaking and microinjection induce cardiovascular toxicity in zebrafish

Zhu¹,

Xu²,

He³

et al. 2013

J of Applied Toxicology

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Cardiovascular toxicity is a major challenge for the pharmaceutical industry and predictive screening models to identify and eliminate pharmaceuticals with the potential to cause cardiovascular toxicity in humans are urgently needed. In this study, taking advantage of the transparency of larval zebrafish, Danio rerio, we assessed cardiovascular toxicity of seven known human cardiotoxic drugs (aspirin, clomipramine hydrochloride, cyclophosphamide, nimodipine, quinidine, terfenadine and verapamil hydrochloride) and two non-cardiovascular toxicity drugs (gentamicin sulphate and tetracycline hydrochloride) in zebrafish using six specific phenotypic endpoints: heart rate, heart rhythm, pericardial edema, circulation, hemorrhage and thrombosis. All the tested drugs were delivered into zebrafish by direct soaking and yolk sac microinjection, respectively, and cardiovascular toxicity was quantitatively or qualitatively assessed at 4 and 24 h post drug treatment. The results showed that aspirin accelerated the zebrafish heart rate (tachycardia), whereas clomipramine hydrochloride, cyclophosphamide, nimodipine, quinidine, terfenadine and verapamil hydrochloride induced bradycardia. Quinidine and terfenadine also caused atrioventricular (AV) block. Nimodipine treatment resulted in atrial arrest with much slower but regular ventricular heart beating. All the tested human cardiotoxic drugs also induced pericardial edema and circulatory disturbance in zebrafish. There was no sign of cardiovascular toxicity in zebrafish treated with non-cardiotoxic drugs gentamicin sulphate and tetracycline hydrochloride. The overall prediction success rate for cardiotoxic drugs and non-cardiotoxic drugs in zebrafish were 100% (9/9) as compared with human results, suggesting that zebrafish is an excellent animal model for rapid in vivo cardiovascular toxicity screening. The procedures we developed in this report for assessing cardiovascular toxicity in zebrafish were suitable for drugs delivered by either soaking or microinjection.

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Zebrafish Xenotransplant Cancer Model for Drug Screening

Cited by 6 publications

References 22 publications

A Zebrafish Thrombosis Model for Assessing Antithrombotic Drugs

A Zebrafish Thrombosis Model for Assessing Antithrombotic Drugs

Human prokinetic drugs promote gastrointestinal motility in zebrafish

Human cardiotoxic drugs delivered by soaking and microinjection induce cardiovascular toxicity in zebrafish

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