Tanshinone IIA sodium sulfonate protects against cardiotoxicity induced by doxorubicin in vitro and in vivo.
Although doxorubicin (DXR) is an effective antineoplastic agent; the serious cardiotoxicity mediated by the production of reactive oxygen species has remained a considerable clinical problem. Our hypothesis is that tanshinone IIA sodium sulfonate (TSNIIA-SS), which holds significant affects on cardioprotection in clinic, protects against DXR-induced cardiotoxicity. In vitro investigation on H9c2 cell line, as well as in vivo study in animal model of DXR-induced chronic cardiomyopathy were performed. TSNIIA-SS significantly increased cell viability and ameliorated apoptosis of DXR-injured H9c2 cells using CCK-8 assay and Hoechst 33342 stain respectively. Furthermore, the cardio-protective effects of TSNIIA-SS were confirmed with decreasing ST-interval and QRS interval by electrocardiography (ECG); improving appearance of myocardium with haematoxylin and eosin (H&E) stain; increasing myocardial tensile strength using tension to rupture (TTR) assay and decreasing fibrosis through picric-sirius red staining comparing with those receiving DXR alone. These data have provided the considerable evidences that TSNIIA-SS is a protective agent against DXR-induced cardiac injury.
Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China. baohong_jiang@yahoo.com.cn
Baohong
B
Jiang
Lin
L
Zhang
Yingchun
Y
Wang
Ming
M
Li
Wanying
W
Wu
Shuhong
S
Guan
Xuan
X
Liu
Min
M
Yang
Junchen
J
Wang
De-an
DA
Guo
D045784:Abietanes; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001562:Benzimidazoles; D002316:Cardiotonic Agents; D002460:Cell Line; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004562:Electrocardiography / Q000187:drug effects; D024022:Fibrillar Collagens / Q000378:metabolism; D005456:Fluorescent Dyes; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D032446:Myoblasts / Q000187:drug effects; D010616:Phenanthrenes / Q000494:pharmacology*; D051381:Rats; D013718:Tensile Strength
D045784:Abietanes; D000903:Antibiotics, Antineoplastic; D001562:Benzimidazoles; D002316:Cardiotonic Agents; D024022:Fibrillar Collagens; D005456:Fluorescent Dyes; D010616:Phenanthrenes; C021751:tanshinone; D004317:Doxorubicin; C017807:bisbenzimide ethoxide trihydrochloride