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Open Access Methodology article

Small molecule screening platform for assessment of cardiovascular toxicity on adult zebrafish heart

Satish Srinivas Kitambi*, Erik S Nilsson, Petra Sekyrova, Cristian Ibarra, Gilbert Nyah Tekeoh, Michael Andäng, Patrik Ernfors and Per Uhlén

Author Affiliations

Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Karolinska Institutet, Stockholm 17177, Sweden

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BMC Physiology 2012, 12:3  doi:10.1186/1472-6793-12-3

Published: 26 March 2012

Abstract

Background

Cardiovascular toxicity is a major limiting factor in drug development and requires multiple cost-effective models to perform toxicological evaluation. Zebrafish is an excellent model for many developmental, toxicological and regenerative studies. Using approaches like morpholino knockdown and electrocardiogram, researchers have demonstrated physiological and functional similarities between zebrafish heart and human heart. The close resemblance of the genetic cascade governing heart development in zebrafish to that of humans has propelled the zebrafish system as a cost-effective model to conduct various genetic and pharmacological screens on developing embryos and larvae. The current report describes a methodology for rapid isolation of adult zebrafish heart, maintenance ex vivo, and a setup to perform quick small molecule throughput screening, including an in-house implemented analysis script.

Results

Adult zebrafish were anesthetized and after rapid decapitation the hearts were isolated. The short time required for isolation of hearts allows dissection of multiple fishes, thereby obtaining a large sample size. The simple protocol for ex vivo culture allowed maintaining the beating heart for several days. The in-house developed script and spectral analyses allowed the readouts to be presented either in time domain or in frequency domain. Taken together, the current report offers an efficient platform for performing cardiac drug testing and pharmacological screens.

Conclusion

The new methodology presents a fast, cost-effective, sensitive and reliable method for performing small molecule screening. The variety of readouts that can be obtained along with the in-house developed analyses script offers a powerful setup for performing cardiac toxicity evaluation by researchers from both academics and industry.

Keywords:
Heart; Screening; Zebrafish; Small molecule; Ex vivo; Ca2+ signaling