Abstract:In clinical practice, more and more attention has been paid to chemotherapy-related cardiotoxicity, which often hinders the optimal treatment of cancer. Anthracyclines (AC) are the most commonly used anticancer drug, which are very effective for hematological malignancies. Although modern imaging techniques can identify patients at risk of AC induced cardiotoxicity (AIC), the therapeutic effect is not good, part of the reason is that the molecular mechanism of AIC is still unclear. Although AIC is initially attributed to cellular oxidative stress, antioxidants do not prevent AIC, suggesting that AIC involves other mechanisms. A series of studies have shown that autophagy may play an important role. This review will summarize the relevant evidence of autophagy in AIC to explore the role of targeted cardiac autophagy in the prevention of AIC.

Abstract:Aim To study the preventive effect and mechanism of ligustrazine on doxorubicin-induced cardiotoxicity in mice. Methods The mouse model of cardiotoxicity induced by doxorubicin was established. The mice were randomly divided into three groups:sham group, doxorubicin group (doxorubicin 15 mg/kg), ligustrazine treated group (ligustrazine 60 mg/(kg·d)＋doxorubicin 15 mg/kg), echocardiography was performed to detect cardiac function of doxorubicin and ligustrazine intervention groups in mice. The sections were stained with HE staining or Massons trichrome staining for histological and collagen analysis, apoptosis of cardiomyocyte were analyzed by TUNEL staining, Western blot was used to analyze the expression of Akt, endothelial nitric oxide synthase (eNOS), the phosphorylation of Akt and eNOS.Results Compared with doxorubicin group, the fractional shortening (FS) and the ventricular ejection fraction (EF) in the ligustrazine treated group were significantly higher (P＜0.01). The ligustrazine treated group significantly decreased apoptosis of cardiomyocyte in mice as compared to the doxorubicin group (P＜0.01), the expression of p-Akt and p-eNOS in the ligustrazine treated group were stronger than those in the the doxorubicin group (P＜0.01). Meanwhile, the ligustrazine treated group significantly inhibited cleaved Caspase-3 as compared to the doxorubicin group. Conclusion Ligustrazine protects doxorubicin-induced myocardial injury by activating Akt/eNOS signaling pathway and inhibiting cardiomyocyte apoptosis, and it may be an underlying mechanism by which ligustrazine can prevent doxorubicin-induced cardiotoxicity.

Abstract:Aim To explore whether oxidative stress mediates doxorubicin-induced cardiotoxicity by inhibiting cystathionine-γ-lyase(CSE) expression and activity. Methods H9c2 cells treated with doxorubicin were used as the model of doxorubicin cardiototoxicity.H9c2 cells were pretreated with N-acetly-L-cysteine(NAC) 60 min prior to treatment with DOX so as to examine the role of oxidative stress in DOX-induced injury.Cell viability was measured by cell counter kit-8.The level of reactive oxygen species(ROS) was tested by dichlorfluorescein staining and photofluorography.Expression of CSE was detected by Western blot assay.Activity of CSE was examined by methylene blue test assay. Results Exposure of H9c2 cells to 5 μmol/L doxorubicin induced significant cardiotoxicity,leading to a decrease in cell viability.Doxorubicin not only enhanced ROS generation,but also inhibited CSE expression and activity in H9c2 cells.Pretreatment with NAC attenuated doxorubicin-induced ROS generation and cardiotoxicity,and also blocked the inhibitory effect of CSE expression and activity by doxorubicin. Conclusion ROS may mediate doxorubicin-induced cardiotoxicity by inhibiting CSE expression and activity.