Establishing a scientific visualization framework to assess drug-induced cardiotoxicity using transgenic zebrafish

Abstract

Drug-induced cardiotoxicity is the leading cause of drug withdrawals from the market. Zebrafish embryos and larvae are suitable as an alternative screening model that can bridge the gap between in vivo mammalian models and in vitro cell-based models, for the early screening of potentially cardiotoxic compounds. Currently, no standardized guideline or framewok is available for the assessment of drug-induced cardiotoxicity in larval zebrafish. Towards this aim, we have established a scientific visualization framework, detailing a set of measurements to graphically illustrate videos of a beating heart, for the assessment of cardiac function. We utilised two transgenic lines, Tg(cmlc2:GCaMP2) and Tg(gata:dsRed), fluorescent microscopy-based high speed optical recording and a free image analysis software, Image J. This framework was validated through the use of 3 known cardiotoxic drugs (Verapamil Hydrochloride, Nifedipine and Doxorubicin hydrochloride) delivered via whole embryo soaking and intravenous microinjection into the sinus venosus. Through this framework, we then determined the cardiotoxic potential of 2 Wnt inhibitors, IWR1 and C59.