Based on the novel anti-heart failure drug ARNI,the mechanism of prevention of cardiotoxicity caused by anthracycline antitumor drugs was discussed
10.3969/j.issn.1006-5725.2024.02.011
- VernacularTitle:沙库巴曲缬沙坦钠片预防多柔比星所致心脏毒性的机制
- Author:
Jieqiong LIU
1
;
Yali YAO
;
Qian SUI
;
Ke LI
;
Fang HUANG
;
Yongqing CAO
Author Information
1. 长沙市第一医院(中南大学湘雅医学院附属长沙医院)血液肿瘤(长沙 410005)
- Keywords:
entresto;
doxorubicin;
cardiotoxicity;
oxidative stress;
mitochondria
- From:
The Journal of Practical Medicine
2024;40(2):188-194
- CountryChina
- Language:Chinese
-
Abstract:
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.
