Food therapy of scutellarein ameliorates pirarubicin-induced cardiotoxicity in rats by inhibiting apoptosis and ferroptosis through regulation of NOX2-induced oxidative stress

作者全名："Lan, Ying; Tian, Fengshun; Tang, Heng; Pu, Peng; He, Quan; Duan, Liang"

作者地址："[Lan, Ying; Tang, Heng; Pu, Peng; He, Quan] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, Chongqing 400042, Peoples R China; [Tian, Fengshun] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrine, Chongqing 400042, Peoples R China; [Duan, Liang] Chongqing Med Univ, Affiliated Hosp 1, Dept Gen Practice, Chongqing 400042, Peoples R China"

通信作者："He, Q (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, Chongqing 400042, Peoples R China.; Duan, L (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Gen Practice, Chongqing 400042, Peoples R China."

来源：MOLECULAR MEDICINE REPORTS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001194087500001

JCR分区：Q2

影响因子：3.4

年份：2024

卷号：29

期号：5

开始页：　

结束页：　

文献类型：Article

关键词：scutellarein; pirarubicin; oxidative stress; apoptosis; ferroptosis; cardiotoxicity

摘要："Pirarubicin (THP) is one of the most commonly used antineoplastic drugs in clinical practice. However, its clinical application is limited due to its toxic and heart-related side effects. It has been reported that oxidative stress, inflammation and apoptosis are closely associated with cardiotoxicity caused by pirarubicin (CTP). Additionally, it has also been reported that scutellarein (Sc) exerts anti-inflammatory, antioxidant, cardio-cerebral vascular protective and anti-apoptotic properties. Therefore, the present study aimed to investigate the effect of food therapy with Sc on CTP and its underlying molecular mechanism using echocardiography, immunofluorescence, western blot, ROS staining, and TUNEL staining. The in vivo results demonstrated that THP was associated with cardiotoxicity. Additionally, abnormal changes in the expression of indicators associated with oxidative stress, ferroptosis and apoptosis were observed, which were restored by Sc. Therefore, it was hypothesized that CTP could be associated with oxidative stress, ferroptosis and apoptosis. Furthermore, the in vitro experiments showed that Sc and the NADPH oxidase 2 (NOX2) inhibitor, GSK2795039 (GSK), upregulated glutathione peroxidase 4 (GPX4) and inhibited THP-induced oxidative stress, apoptosis and ferroptosis. However, cell treatment with the ferroptosis inhibitor, ferrostatin-1, or inducer, erastin, could not significantly reduce or promote, respectively, the expression of NOX2. However, GSK significantly affected ferroptosis and GPX4 expression. Overall, the results of the present study indicated that food therapy with Sc ameliorated CTP via inhibition of apoptosis and ferroptosis through regulation of NOX2-induced oxidative stress, thus suggesting that Sc may be a potential therapeutic drug against CTP."

基金机构：National Key R&D Program of China

基金资助正文：Not applicable.