Human prokinetic drugs promote gastrointestinal motility in zebrafish

Zhou, Jiali; Guo, Sheng-Ya; Zhang, Y.; Li, Chunqian

doi:10.1111/nmo.12306

Cited by 40 publications

(27 citation statements)

References 30 publications

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“…Zebrafish is emerging as a predictive animal model for in vivo assessment of drug efficacy, toxicity, and safety. 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.…”

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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“…According to our laboratory quality control standard, successful experiments must meet these milestones: (1) zebrafish natural death in untreated (control) groups was ≤10%; and (2) intraplate and interplate coefficients of variation (CV) were ≤25% (Zhou et al, 2014).…”

Section: Quality Control Standardmentioning

confidence: 99%

Toxicity comparison of different active fractions extracted from radix Sophorae tonkinensis in zebrafish

Liu

Zhu²,

Chen

et al. 2017

J. Zhejiang Univ. Sci. B

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Abstract:Radix Sophorae tonkinensis (RST) is a widely used herb in Traditional Chinese Medicine (TCM) for treating infectious and inflammatory diseases. However, the toxicity data for RST are limited. The aim of this work is to assess and compare the toxicity of the whole RST extract and its five active fractions using the zebrafish model. Five active fractions of RST were prepared using five different types of solvents, which included dealkalized water, ethanol, n-butyl ethanol, dichloromethane, and diethyl ether. The chemical profiles of the active fractions were determined by high-performance liquid chromatography (HPLC), and the toxicity observed in the zebrafish model was confirmed using mouse models. In the zebrafish model, cardiovascular toxicity was observed for the fraction extracted using diethyl ether, and hepatotoxicity was observed for the whole RST extract and the fractions extracted using water and ethanol, whereas both cardiovascular and hepatic toxicities were observed for the fractions extracted using n-butyl ethanol and dichloromethane. The hepatotoxicity of the fractions extracted using n-butyl ethanol and dichloromethane was also observed in mice. Our findings provide the toxicity data for RST and its five active fractions through modeling in a zebrafish, and indicate that the different fractions may each have a different toxicity, which is helpful for the optimal use of RST in clinical practice.

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“…TTX and carbachol were dissolved in 0.9% saline, whereas benzbromarone was dissolved in dimethyl sulfoxide (DMSO). To minimize any potential effects of the solvent, we ensured that the final concentration of DMSO in the bath did not exceed 0.1% (v/v), as this concentration has been previously shown to have no effects on gastrointestinal motility in a range of in vitro and in vivo studies on fish (Jensen and Conlon, 1997;Shahbazi et al, 1998;Zhou et al, 2014). Video recordings were analyzed by importing files into Volumetry G8d to construct spatiotemporal maps (ST maps).…”

Section: Recording and Analysis Of Gastrointestinal Motility Patternsmentioning

confidence: 99%

The presence and role of interstitial cells of Cajal in the proximal intestine of shorthorn sculpin (Myoxocephalus scorpius)

Brijs

Hennig

Kellermann

et al. 2016

Journal of Experimental Biology

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Rhythmic contractions of the mammalian gastrointestinal tract can occur in the absence of neuronal or hormonal stimulation owing to the generation of spontaneous electrical activity by interstitial cells of Cajal (ICC) that are electrically coupled to smooth muscle cells. The myogenically driven component of gastrointestinal motility patterns in fish probably also involves ICC; however, little is known of their presence, distribution and function in any fish species. In the present study, we combined immunohistochemistry and in vivo recordings of intestinal motility to investigate the involvement of ICC in the motility of the proximal intestine in adult shorthorn sculpin (Myoxocephalus scorpius). Antibodies against anoctamin 1 (Ano1, a Ca 2+ -activated Cl − channel), revealed a dense network of multipolar, repeatedly branching cells in the myenteric region of the proximal intestine, similar in many regards to the mammalian ICC-MY network. The addition of benzbromarone, a potent blocker of Ano1, altered the motility patterns seen in vivo after neural blockade with TTX. The results indicate that ICC are integral for the generation and propagation of the majority of rhythmic contractile patterns in fish, although their frequency and amplitude can be modulated via neural activity.

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Human prokinetic drugs promote gastrointestinal motility in zebrafish

Abstract: These results suggest that larval zebrafish motility model developed here is a useful tool for whole-animal in vivo GI transit studies and for assessing prokinetic drugs.

Cited by 40 publications

References 30 publications

A Zebrafish Thrombosis Model for Assessing Antithrombotic Drugs

A Zebrafish Thrombosis Model for Assessing Antithrombotic Drugs

Toxicity comparison of different active fractions extracted from radix Sophorae tonkinensis in zebrafish

The presence and role of interstitial cells of Cajal in the proximal intestine of shorthorn sculpin (Myoxocephalus scorpius)

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