Background: One of the common adverse reactions to anthracyclines, a group of chemotherapeutics, is cardiotoxicity. Cancer patients receiving anthracycline-based chemotherapeutic regimens often discontinue treatment due to cardiotoxicity. How to prevent and reduce the cardiotoxicity of anthracyclines is one of the hot topics in the field of onco-cardiology. Traditional Chinese medicine can reduce the toxic side effects of chemotherapeutics. The present study aimed to investigate the protective effect of Qishen Huanwu capsule (QSHWC) on pirarubicin (THP)-induced myocardial injury in rats and the underlying mechanisms.
Methods: Forty-eight male Sprague-Dawley (SD) rats were randomly divided into six groups: control group, THP, low-dose QSHWC, moderate-dose QSHWC, high-dose QSHWC, and LY294002 [phosphatidylinositol 3-kinase (PI3K) inhibitor] (n=8 each). Echocardiographic examination was performed to examine heart structure and function. Hematoxylin and eosin (HE) staining was conducted to examine histopathological changes in myocardial tissue. Immunofluorescence staining was carried out to examine the expression of the autophagosome-specific marker protein microtubule-associated protein 1 light chain 3 (LC3). Western blot was performed to analyze the expression of LC3-I, LC3-II, PI3K, phosphorylated (p)-PI3K, protein kinase B (Akt), p-Akt, mammalian target of rapamycin (mTOR), and p-mTOR.
Results: Compared with the control group, the THP group had a higher left ventricular end-systolic diameter (LVESD), lower left ventricular ejection fraction (LVEF), lower left ventricular fractional shortening (LVFS), and inferior heart function. In addition, compared with the control group, the THP group had significantly higher LC3 protein expression, a significantly higher LC3-II/LC3-I ratio (P<0.05), and significantly lower p-PI3K, p-Akt, and p-mTOR (P<0.05). QSHWC attenuated the THP-induced decline in heart function, downregulated LC3 protein in rat myocardial tissue, decreased the LC3-II/LC3-I ratio, and increased p-PI3K, p-Akt, and p-mTOR. In the LY294002 group, the above effects of QSHWC were reversed.
Conclusions: QSHWC alleviated THP-induced myocardial injury. The underlying mechanism was related to the activation of the PI3K/Akt/mTOR pathway and the mitigation of the excessive autophagy of cardiomyocytes caused by THP.
Keywords: Qishen Huanwu capsule (QSHWC); autophagy; cardiotoxicity; phosphatidylinositol 3-kinase/ protein kinase B/mammalian target of rapamycin signaling pathway (PI3K/Akt/mTOR signaling pathway); pirarubicin.