Scutellarin Attenuates Doxorubicin-Induced Cardiotoxicity by Inhibiting Myocardial Fibrosis,Apoptosis and Autophagy in Rats |
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Authors: | Xipeng Sun Li Zhou Yonglong Han Quanjun Yang Xingxia Li Bo Xin Mengyi Chi Yaxian Wang Cheng Guo |
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Institution: | 1. Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233 China;2. Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233 China
College of Food Science & Technology, Shanghai Ocean University, Shanghai, 201306 China
These authors contributed equally to this work. |
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Abstract: | The anthracycline antibiotic doxorubicin (DOX) is an effective anticancer agent, but its clinical use is limited by dose-dependent cardiotoxicity. Scutellarin (SCU), a natural polyphenolic flavonoid, is used as a cardioprotective agent for infarction and ischemia-reperfusion injury. This study investigated the beneficial effect of SCU on DOX-induced chronic cardiotoxicity. Rats were injected intraperitoneally (i. p.) with DOX (2.5 mg/kg) twice a week for four weeks and then allowed to rest for two weeks to establish the chronic cardiotoxicity animal model. A dose of 10 mg/kg/day SCU was injected i. p. daily for six weeks to attenuate cardiotoxicity. SCU attenuated DOX-induced elevated oxidative stress levels and cardiac troponin T (cTnT), decreased left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), elevated isovolumic relaxation time (IVRT), electrophysiology and histopathological alterations. In addition, SCU significantly attenuated DOX-induced cardiac fibrosis and reduced extracellular matrix (ECM) accumulation by inhibiting the TGF-β1/Smad2 signaling pathway. Furthermore, SCU also prevented against DOX-induced apoptosis and autophagy as evidenced by upregulation of Bcl-2, downregulation of Bax and cleaved caspase-3, inhibited the AMPK/mTOR pathway. These results revealed that the cardioprotective effect of SCU on DOX-induced chronic cardiotoxicity may be attributed to reducing oxidative stress, myocardial fibrosis, apoptosis and autophagy. |
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Keywords: | scutellarin doxorubicin cardiotoxicity myocardial fibrosis apoptosis autophagy |
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