Zebrafish Enterotoxicity Assays

Gastrointestinal intolerance is a common preclinical finding and can be a serious clinical safety concern. Mammalian GI responsibility testing comes at the expense of time, test items, and labor. The study found that the zebrafish gastrointestinal (GI) tract is similar to the mammalian gastrointestinal tract in terms of gene expression, nervous system control, and response to chemical challenges. Zebrafish have been widely used to model intestinal diseases, including the study of microbiome effects, congenital diseases, intestinal inflammation, enteric nervous system, movement disorders, and intestinal tumors.

Several reports have emerged of the use of zebrafish in drug development to detect the potential enterotoxicity of compounds, focusing on assessing the predictive value of zebrafish for enterotoxicity. These reports tested the effects of marketed drugs with and without gastrointestinal effects on intestinal contractility or transit time in zebrafish. According to these reports, zebrafish are expected to identify more than 50% of toxic compounds found as a first-level screen for enterotoxicity, thereby prioritizing safer compounds for mammalian testing.

Fig. 1 Imaging of zebrafish gut motility.

Our Zebrafish Enterotoxicity Assays

Drawing on years of experience and advanced technology, Creative Biogene has developed a high-throughput method for predicting mammalian gastrointestinal safety issues using larval zebrafish. Our improved zebrafish gut motility imaging and gut transit time measurement methods enable higher sensitivity and throughput for toxicology. Results from our pre-test experiments demonstrated good correlation between the effects of some compounds in our zebrafish models and data from other in vivo models or known clinical adverse effects. For gut function, our zebrafish assays have the potential to predict adverse drug reactions and support their possible role in the early safety assessment of new compounds.

Our Advantages

• Allows screening of a large number of different compounds against many different and related toxicity endpoints.
• Ability to characterize GI motor patterns in a complete physiological context.
• Tracking the movement of macrophages within the smooth muscle layer of the gastrointestinal tract in vivo.
• Allows non-invasive examination of organ development and toxicity endpoints
• Fast and accurate identification of drugs that are toxic to the digestive system

Contact us to learn more about our zebrafish enterotoxicity assays services.

References

1. Zhao X, et al. Modeling intestinal disorders using zebrafish. Methods Cell Biol.2017,138:241-270.
2. Cassar S, et al. A high-throughput method for predicting drug effects on gut transit time using larval zebrafish. J Pharmacol Toxicol Methods. 2015,76:72-75.
3. Rich A. Improved Imaging of Zebrafish Motility. Neurogastroenterol Motil. 2018, 30(9):e13435.
4. Berghmans S, et al. Zebrafish based assays for the assessment of cardiac, visual and gut function--potential safety screens for early drug discovery. J Pharmacol Toxicol Methods. 2008, 58(1):59-68.
5. Cassar S, et al. Use of Zebrafish in Drug Discovery Toxicology. Chem Res Toxicol. 2020, 33(1):95-118.

For research use only. Not intended for any clinical use.