Pharmacological assessment of zebrafish-based cardiotoxicity models.

Monika Maciag, Artur Wnorowski, Malgorzata Mierzejewska, Anita Plazinska

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2022 Apr

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Cardiotoxicity remains the most common reason for failure during drug development. Recently, the zebrafish (Danio rerio) model has emerged for the evaluation of drug-dependent cardiotoxicity and for the identification of cardioprotective molecules. However, it remains unknown how closely the zebrafish-based results may be translated to humans. To tackle this issue, we established embryonic zebrafish models of doxorubicin-, adrenaline- and terfenadine-induced cardiotoxicity with unified dosing regimen which eventually enabled head-to-head comparison of the drugs. Subsequently, we determined whether human cardioprotective medications - dexrazoxane, metoprolol, carvedilol and valsartan - are able to manage heart dysfunction in zebrafish. Our results indicated that doxorubicin, adrenaline and terfenadine elicited overt signs of cardiotoxicity in fish, and we further showed that the blockade of the renin-angiotensin system and, to a lesser extent, β-adrenergic system, ameliorated the heart disease in zebrafish. From the drug development standpoint, our work opens the possibility to determine the cardiovascular properties of tested compounds using the rapid and affordable zebrafish model. Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Citation

Monika Maciag, Artur Wnorowski, Malgorzata Mierzejewska, Anita Plazinska. Pharmacological assessment of zebrafish-based cardiotoxicity models. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022 Apr;148:112695