心脏毒性
药理学
阿霉素
灯盏乙素
心肌纤维化
自噬
化学
纤维化
癌症研究
医学
细胞凋亡
内科学
毒性
化疗
生物化学
有机化学
色谱法
作者
Xipeng Sun,Li Zhou,Yonglong Han,Quanjun Yang,Xingxia Li,Xin Bo,Mengyi Chi,Yaxian Wang,Cheng Guo
标识
DOI:10.1002/cbdv.202200450
摘要
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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