Abstract
QiShenYiQi Pills (QSYQ) is a compound Chinese medicine used for treatment of cardiovascular diseases. The present study investigated the effects of QSYQ on the Doxorubicin- (DOX-) induced disorders in rat cardiac structure and function and the possible mechanism underlying. A total of 24 male Sprague-Dawley rats were administrated by intraperitoneal injections with DOX at a dose of 2.5 mg/kg, once every day for a total of 6 times. After the 6th injection, the rats were evaluated by echocardiographic analysis, and the animals with injured heart (n = 14) were divided into 2 groups and further treated with (n = 7) or without (n = 7) QSYQ by gavage at a dose of 0.2 g/day, once a day, over the next 2 weeks. Two weeks after QSYQ treatment, the following variables were assessed: myocardial blood flow (MBF) by Laser-Doppler Perfusion Imager, the ratio of heart weight to body weight (HW/BW), myocardial histology, myocardial content of ATP, AMP, free fatty acids (FFAs) and AMP/ATP by ELISA, and expression of PPARα, PGC-1α, and ATP 5D by Western blot. Statistical analysis was performed using one-way ANOVA followed by Turkey test for multiple comparisons. DOX challenge significantly increased left ventricular internal diameter and HW/BW and decreased the thickness of the left ventricular posterior wall, the left ventricle ejection fraction, and the left ventricle fractional shortening. DOX also increased AMP, FFA, and AMP/ATP, decreased ATP, and downregulated the protein content of ATP 5D, PPAR α, and PGC-1 α. All these DOX-induced cardiac insults were attenuated significantly by QSYQ treatment. These results show the potential of QSYQ to ameliorate DOX-induced disorders in cardiac structure and function; this effect may be related to the increase in myocardial ATP content via the upregulation of ATP 5D, PPAR α, and PGC-1 α and the oxidation of FFA.
Highlights
Cancer and cardiovascular diseases (CVDs) have become the main cause of death for the adults in China [1]
QiShenYiQi Pills (QSYQ) is a compound Chinese medicine used for treatment of cardiovascular diseases. e present study investigated the effects of QSYQ on the Doxorubicin- (DOX-) induced disorders in rat cardiac structure and function and the possible mechanism underlying
Evidence-Based Complementary and Alternative Medicine published with respect to the mechanism responsible for the cardiac toxicity of DOX. e myocardial damage caused by DOX is reported to be relevant to free radicals [5], iron ion unbalanced metabolism [6], calcium overload [7], mitochondria damage [8], and cell apoptosis [9]
Summary
Cancer and cardiovascular diseases (CVDs) have become the main cause of death for the adults in China [1]. Coactivation of PGC-1 αα and PPAR αα can regulate FAO [12], which plays an important role in cardiac energy metabolism and injury. Hang et al con rmed that QSYQ can protect against cardiac injury and brosis in ischemia-reperfusion rat and increase the expression of vascular endothelial growth factor (VEGF) [15]. It is not clear whether QSYQ can reduce DOX-induced cardiac disorder in structure and function, and, if yes, what is the underlying mechanism? E present study was conducted to address the effect of QSYQ on DOX-induced disorder by testing ATP, ATP 5D, F-actin, PPAR αα, and PGC-1 αα in rat heart
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