Original Article

Protective effect of tetrahydroxystilbene glucoside on cardiotoxicity induced by doxorubicin in vitro and in vivo

Authors: Shao-hui Zhang, Wen-quan Wang, Jia-ling Wang
DOI: 10.1038/aps.2009.144

Abstract

Aim: To test the effect of 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) on doxorubicin (DOX)-induced cardiotoxicity.
Methods: We used neonate rat cardiomyocytes and an acute mouse model of DOX-induced cardiotoxicity to examine the protective effect of THSG.
Results: In the mouse model, administration of THSG significantly reduced DOX-induced cardiotoxicity, including animal mortality, histopathological changes, and levels of serum creatine kinase (CK) and lactate dehydrogenase (LDH). Moreover, THSG was able to attenuate the increased malondialdehyde (MDA) and decreased reduced glutathione (GSH) caused by DOX. In in vitro studies, THSG 10−300 μmol/L ameliorated DOX-induced cardiomyocyte apoptosis in a concentration-dependent manner. Further studies showed that THSG inhibited reactive oxygen species (ROS) generation and prevented DOX-induced loss of mitochondrial membrane potential, caspase-3 activation and upregulation of Bax protein expression. We observed a protective response against damage after DOX treatment. The level of Bcl-2 protein was increased. Additionally, THSG inhibited a DOX-induced [Ca2+] increase.
Conclusion: These results showed that THSG protected against DOX-induced cardiotoxicity by decreasing ROS generation and intracellular [Ca2+] and by inhibiting apoptotic signaling pathways.
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