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Protective effects of sodium tanshinone II A sulfonate against sunitinib induced cardiotoxicity in H9c2 cell and zebrafish

English Abstract

One of the life-threatening side effects of sunitinib-based chemotherapy is cardiotoxicity; the mechanism leading to cardiatoxicity in vivo induced by sunitinib is still a current unmet need. However, only limited datas are available in the literature regarding to the prevention and protection against sunitinib induced cardiotoxicity. Here we investigated cardiac toxicity of sunitnib at early life stage of zebrafish and the protective effects of sodium tanshinoneⅡA sulfonate (STS) against it. Firstly, we found that sunitinib caused embryo heart dysfunction in a dose-dependent manner. Most importantly, sunitinib also caused a significant decrease in the total number of cardiomyocytes. Gene analysis results demonstrated that sunitinib unregulated endothelin-1 mRNA expression. In addition, sunitinib demonstrated profound effects on Cai 2+ transients in zebrafish cardiomyocytes and human cardiomyocytes. The results showed us that sunitinib caused heart function disorder in zebrafish model at early life stage and cardiotoxicity maybe a high risk factor when children was suffering sunitinib based therapeutic, Based on the information above, sodium tanshinoneⅡA sulfonate used to treat cardiovascular disease in China for many years was combined with sunitinib to explore the protection effect on the toxicity induced by sunitinib in vitro H9c2 cell 2 and in vivo in zebrafish models. We discovered that H9c2 cells exposed to sunitinib leaded to a significant reduction in cell viability and an increase in intracellular calcium. Zebrafish exposed to sunitinib caused a decrease in heart rate accompanied by an increase in the ratio of SA-BV distance to body length at 96 hpf, which were consistent with the in vitro data. Sodium tanshinoneⅡA sulfonate corrected the altered parameters-induced by sunitinib. It suggested that sodium tanshinoneⅡA sulfonate could prevent sunitinib-induced H9c2 cell injury and sunitinib-stimulated cardiac dysfunction in zebrafish. The cardioprotective effects of sodium tanshinoneⅡA sulfonate may be correlated with calcium homeostasis. In the present study, we established a simple and reproducible cardiotoxicity model induced by the anticancer therapeutic agent sunitinib malate in zebrafish embryos and explored the underlying pathophysiological mechanism. At the same time, we found that sodium tanshinoneⅡA sulfonate showed protective effects in vitro H9c2 cell and in vivo zebrafish models.

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Huang, Xiao Hui


Institute of Chinese Medical Sciences




Heart -- Disease -- Treatment

Heart -- Disease -- Prevention

Chinese Medicinal Science -- Institute of Chinese Medical Sciences

中藥學 -- 中華醫藥研究院


Lee, MingYuen

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