D6.1 Cardiac toxicity of compounds as determined by combined MEA/impedance measurements
The present deliverable describes the results of multi-electrode array and impedance studies in human cardiomyocytes, treated with doxorubicin. Doxorubicin is an antineoplastic drug which causes acute and chronic toxicity. The most dangerous side effect of doxorubicin is cardiomyopathy, leading to congestive heart failure. Effects were assessed after a short and long exposure with a following washout period. The obtained data show major effects with long-term arrhythmicity in beating. Especially higher concentrations indicate a strong decrease in the beating frequency. These observations could be detected by both MEA and impedance measurements. Moreover, exposure to doxorubicin at higher concentrations significantly decreased the number of surviving cells during a long-term treatment. The effect of doxorubicin in short exposure could be washed out, however after long exposure the decrease in beating frequency seems to be irreversible. Altogether, the study indicates that decrease in cell survival and increase in arrhythmia, described as important failures of doxorubicin-induced cardiotoxicity, were successfully detected by both MEA and impedance systems. It may serve as a predictive biomarker related to key events in cardiotoxity induced by drugs or other chemical substances.
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D9.5 Report on analogs of the DETECTIVE biomarkers of hepatotoxicity and comparison with in vivo RDT data
D10.1 Complete atlas of gene expression signatures and functional annotations