Scutellarin attenuated doxorubicin-induced chronic cardiotoxicity in rats by reducing oxidative stress, myocardial fibrosis, apoptosis, and autophagy.
Does scutellarin attenuate doxorubicin-induced chronic cardiotoxicity in a rat model?
In a rat model, scutellarin demonstrated cardioprotective effects against doxorubicin-induced chronic cardiotoxicity by reducing oxidative stress, myocardial fibrosis, apoptosis, and autophagy.
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.
Sun et al. (Thu,) conducted a other in Doxorubicin-induced chronic cardiotoxicity. Scutellarin vs. Doxorubicin alone was evaluated on Cardiotoxicity markers (oxidative stress, cTnT, LVEF, LVFS, IVRT, fibrosis, apoptosis, autophagy). Scutellarin attenuated doxorubicin-induced chronic cardiotoxicity in rats by reducing oxidative stress, myocardial fibrosis, apoptosis, and autophagy.