Protective effect of tetrahydroxystilbene glucoside on cardiotoxicity induced by doxorubicin in vitro and in vivo.
OBJECTIVE
To test the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-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 micromol/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 [Ca(2+)] increase.


CONCLUSIONS
These results showed that THSG protected against DOX-induced cardiotoxicity by decreasing ROS generation and intracellular [Ca(2+)] and by inhibiting apoptotic signaling pathways.
Zhang
Shao-hui
SH
Department of Pharmacology, Institute of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Wang
Wen-quan
WQ
Wang
Jia-ling
JL
D000818:Animals; D000831:Animals, Newborn; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D005960:Glucosides / Q000008:administration & dosage / Q000494:pharmacology*; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D005960:Glucosides; D017382:Reactive Oxygen Species; D013267:Stilbenes; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside; D004317:Doxorubicin; D002118:Calcium