The Journal of Practical Medicine >
Based on the novel anti-heart failure drug ARNI， the mechanism of prevention of cardiotoxicity caused by anthracycline antitumor drugs was discussed
Received date: 2023-07-12
Online published: 2024-03-06
Objective To explore the efficacy of a new anti?heart failure drug， Entresto， in the prevention of cardiotoxicity caused by doxorubicin （DOX）. Methods Male adult ICR mice were randomly divided into three groups （n = 8）： control group， DOX group and DOX plus Entresto group. Cardiac function of mice was measured by echocardiography. H9c2 cells were pretreated with Entresto （0 - 48 μmol/L） for 24 hours in the presence or absence of DOX （1 mmol/L）， and then cell viability， oxidative stress， apoptosis and mitochondrial function were evaluated. Results As compared with the control group， leakage of CK， CK?MB and LDH increased significantly in the DOX group （P < 0.01）， and left ventricular systolic dysfunction occurred. Entresto administration reversed these changes in the DOX group. The level of ROS and the number of apoptotic cells in cardiomyocytes in the DOX plus Entresto group were lower than those in the DOX group （P < 0.05）. As compared with the DOX group， the level of ROS and the number of apoptotic cells in H9c2 cells decreased significantly in the Entresto plus DOX group （P < 0.05）， and mitochondrial membrane potential increased significantly （P < 0.05）. Entresto reversed the inhibitory effect of DOX on SIRT1/PGC?1α/MFN2 signaling pathway. Conclusions Entresto improves DOX?induced cardiotoxicity by inhibiting ROS?mediated oxidative stress and apoptosis， and its mechanism may be related to SIRT1/PGC?1α/MFN2 signal transduction pathway.
Key words： entresto; doxorubicin; cardiotoxicity; oxidative stress; mitochondria
Jieqiong LIU , Yali YAO , Qian SUI , Ke LI , Fang HUANG , Yongqing. CAO . Based on the novel anti-heart failure drug ARNI， the mechanism of prevention of cardiotoxicity caused by anthracycline antitumor drugs was discussed[J]. The Journal of Practical Medicine, 2024 , 40(2) : 188 -194 . DOI: 10.3969/j.issn.1006-5725.2024.02.011
| 1 | 邱佳， 丁波泥， 钱立元， 等. 紫衫烷类与蒽环类药物用药顺序不同对乳腺癌新辅助化疗疗效影响的meta分析［J］. 重庆医学， 2021， 50（21）： 3720-3725. doi:10.3969/j.issn.1671-8348.2021.21.025 |
| 2 | SYAHPUTRA R A， HARAHAP U， DALIMUNTHE A， et al. The role of flavonoids as a cardioprotective strategy against doxorubicin-induced cardiotoxicity： a review［J］. Molecules， 2022， 27（4）： 1320. doi:10.3390/molecules27041320 |
| 3 | CHRISTIDI E， BRUNHAM L R. Regulated cell death pathways in doxorubicin-induced cardiotoxicity［J］. Cell Death Dis， 2021， 12（4）： 339. doi:10.1038/s41419-021-03614-x |
| 4 | 吴勤研， 王楠， 冷静， 等. 右雷佐生在预防表柔比星心脏毒性时使用的合理性分析［J］. 安徽医药， 2019， 23（11）： 2296-2298. doi:10.3969/j.issn.1009-6469.2019.11.047 |
| 5 | 向长铁， 刘佳丽， 张爱民， 等. 沙库巴曲缬沙坦钠片通过NF2/Mst1信号通路抑制细胞凋亡改善心肌梗死大鼠心肌纤维化［J］. 中国老年学杂志， 2022， 42（8）： 1927-1931. doi:10.3969/j.issn.1005-9202.2022.08.043 |
| 6 | DINDA? F， GüNG?R H， EKICI M， et al. Angiotensin receptor-neprilysin inhibition by sacubitril/valsartan attenuates doxorubicin-induced cardiotoxicity in a pretreatment mice model by interfering with oxidative stress， inflammation， and Caspase 3 apoptotic pathway［J］. Anatol J Cardiol， 2021， 25（11）： 821-828. doi:10.5152/anatoljcardiol.2021.356 |
| 7 | DING M， SHI R， CHENG S， et al. Mfn2-mediated mitochondrial fusion alleviates doxorubicin-induced cardiotoxicity with enhancing its antEntrestoncer activity through metabolic switch［J］. Redox Biol， 2022， 52： 102311. doi:10.1016/j.redox.2022.102311 |
| 8 | YEH J N， YUE Y， CHU Y C， et al. Entresto protected the cardiomyocytes and preserved heart function in cardiorenal syndrome rat fed with high-protein diet through regulating the oxidative stress and Mfn2-mediated mitochondrial functional integrity［J］. Biomed Pharmacother， 2021， 144： 112244. doi:10.1016/j.biopha.2021.112244 |
| 9 | SUO Y， YUAN M， LI H， et al. Sacubitril/valsarEntrestomproves left atrial and left atrial appendage function in patients with atrial fibrillation and in pressure overload-induced mice［J］. Front Pharmacol， 2019， 10： 1285. doi:10.3389/fphar.2019.01285 |
| 10 | SUN X， SUN P， ZHEN D， et al. Melatonin alleviates doxorubicin-induced mitochondrial oxidative damage and ferroptosis in cardiomyocytes by regulating YAP expression［J］. Toxicol Appl Pharmacol， 2022， 437： 115902. doi:10.1016/j.taap.2022.115902 |
| 11 | RAJ P， SAYFEE K， PARIKH M， et al. Comparative and combinatorial effects of resveratrol and sacubitril/valsartan alongside valsartan on cardiac remodeling and dysfunction in MI-induced rats［J］. Molecules， 2021， 26（16）： 5006. doi:10.3390/molecules26165006 |
| 12 | JEREMIC J， GOVORUSKINA N， BRADIC J， et al. Sacubitril/valsartan reverses cardiac structure and function in experimental model of hypertension-induced hypertrophic cardiomyopathy［J］. Mol Cell Biochem， 2023，478（12）：2645-2656. doi:10.1007/s11010-023-04690-7 |
| 13 | RAWAT P S， JAISWAL A， KHURANA A， et al. Doxorubicin-induced cardiotoxicity： An update on the molecular mechanism and novel therapeutic strategies for effective management［J］. Biomed Pharmacother， 2021， 139： 111708. doi:10.1016/j.biopha.2021.111708 |
| 14 | SONGBO M， LANG H， XINYONG C， et al. Oxidative stress injury in doxorubicin-induced cardiotoxicity［J］. Toxicol Lett， 2019， 307： 41-48. doi:10.1016/j.toxlet.2019.02.013 |
| 15 | HAFEZ H M， HASSANEIN H. Montelukast ameliorates doxorubicin-induced cardiotoxicity via modulation of p-glycoprotein and inhibition of ROS-mediated TNF-α/NF-κB pathways［J］. Drug Chem Toxicol， 2022， 45（2）： 548-559. doi:10.1080/01480545.2020.1730885 |
| 16 | HU B， ZHEN D， BAI M， et al. Ethanol extracts of Rhaponticum uniflorum （L.） DC flowers attenuate doxorubicin-induced cardiotoxicity via alleviating apoptosis and regulating mitochondrial dynamics in H9c2 cells［J］. J Ethnopharmacol， 2022， 288： 114936. doi:10.1016/j.jep.2021.114936 |
| 17 | ZHANG Q， ZHANG Y， XIE B， et al. Resveratrol activation of SIRT1/MFN2 can improve mitochondria function， alleviating doxorubicin-induced myocardial injury［J］. Cancer Innovation， 2023， 2（4）： 253-264. doi:10.1002/cai2.64 |
| 18 | WANG J， ZHANG J， XIAO M， et al. Molecular mechanisms of doxorubicin-induced cardiotoxicity： novel roles of sirtuin 1-mediated signaling pathways［J］. Cell Mol Life Sci， 2021， 78（7）： 3105-3125. doi:10.1007/s00018-020-03729-y |
| 19 | CUI W， WU X， SHI Y， et al. 20-HETE synthesis inhibition attenuates traumatic brain injury-induced mitochondrial dysfunction and neuronal apoptosis via the SIRT1/PGC-1α pathway： A translational study［J］. Cell Proliferation， 2021， 54（2）： e12964. doi:10.1111/cpr.12964 |
| 20 | KUNO A， HOSODA R， TSUKAMOTO M， et al. SIRT1 in the cardiomyocyte counteracts doxorubicin-induced cardiotoxicity via regulating histone H2AX［J］. Cardiovasc Res， 2023， 118（17）： 3360-3373. doi:10.1093/cvr/cvac026 |
/
| 〈 |
|
〉 |