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.
Jiang
Baohong
B
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
Zhang
Lin
L
Wang
Yingchun
Y
Li
Ming
M
Wu
Wanying
W
Guan
Shuhong
S
Liu
Xuan
X
Yang
Min
M
Wang
Junchen
J
Guo
De-an
DA
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