Evaluating a novel cardioprotective agent against DOX-induced cardiotoxicity in transgenic zebrafish model

Abstract

Doxorubicin (DOX) is an anticancer drug which has been widely used and become one of the most prescribed antineoplastic agent due to its high efficacy in fighting a wide array of cancers. However, its usage is greatly limited by its well-known side effect, cardiotoxicity. DOX-induced cardiotoxicity was believed due to its cumulative dosage yet mechanisms in cancer fighting and heart damaging were remain controversial. Evidences shown in various studies supported that therapeutic mechanism and mechanism of cardiotoxicity were through different pathways. With that, strategies in developing cardioprotective agent against DOX-induced cardiotoxicty were carried out intensively. In this project, Compound K (CK), a novel cardioprotective agent derived from ginseng was proposed to be effective in attenuating DOX-induced cardiotoxicity. The investigation was done in transgenic zebrafish model. Transgenic zebrafish model has showed advantages in assessing drug toxicity with its body transparency and after integration of fluorescent protein into specific gene promoter, detail morphology of living tissues can be visualized easier as compared to other animal models. Furthermore, more evaluations on cardiac functions were also available with transgenic zebrafish. The results shown indicated CK might be useful as a cardioprotective agent in alleviating cardiotoxicity. Yet, further study is needed to fully understand its protective mechanism and determine its minimum concentration to protect the heart.