HydroMg alleviates doxorubicin-induced chronic cardiotoxicity by attenuating oxidative stress and improving mitochondrial function
10.12025/j.issn.1008-6358.2026.20260058
- VernacularTitle:HydroMg通过减轻氧化应激与改善线粒体功能缓解阿霉素慢性心脏毒性
- Author:
Lu ZHANG
1
;
Xiurui MA
2
;
Yawei JIN
3
;
Yuning ZHANG
3
;
Xiong GAO
3
;
Mohan LI
3
;
Ze YUAN
3
;
Yihua LU
3
;
Wenjiang DING
4
;
Zhiguang DING
5
;
Xiaolei SUN
3
;
Chunxiao ZHANG
6
;
Jian AN
7
Author Information
1. Shanxi Medical University, Taiyuan 030001, Shanxi, China.
2. Department of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan 030001, Shanxi, China.
3. Department of Cardiology, Zhongshan Hospital, Fudan University; Shanghai Institute of Cardiovascular Diseases; State Key Laboratory of Cardiology; National Health Commission Key Laboratory of Ischemic Heart Disease; Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences; National Clinical Research Center for Interventional Medicine, Shanghai 200032, China.
4. Shanghai Jiao Tong University, Shanghai 200240, China.
5. Shanghai HydroMg Health Technology Co., Ltd., Shanghai 200241, China.
6. Department of Cardiology, Shengli Oilfield Central Hospital, Dongying 257034, Shandong, China.
7. Shanxi Medical University, Taiyuan 030001, Shanxi, China;Department of Cardiology, Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China.
- Publication Type:Originalarticle
- Keywords:
HydroMg;
doxorubicin;
chronic cardiotoxicity;
oxidative stress;
mitochondrial function
- From:
Chinese Journal of Clinical Medicine
2026;33(4):582-591
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effect and underlying mechanisms of HydroMg, a novel sustained-release hydrogen donor, in a model of doxorubicin (DOX)-induced chronic cardiotoxicity. Methods H9C2 cells were treated with 1 μmol/L DOX and/or 1 μg/mL HydroMg, and mitochondrial membrane potential, reactive oxygen species (ROS) levels, and apoptosis were measured. In the animal experiment, mice were divided into control, HydroMg, DOX, and DOX＋HydroMg groups. The HydroMg group received intraperitoneal injection of HydroMg (100 mg/kg). Chronic cardiotoxicity was established by intraperitoneal injection of DOX (5 mg/kg every week) for four consecutive weeks; In the DOX＋HydroMg group, HydroMg (100 mg/kg) was administered intraperitoneally 4–5 h prior to each DOX injection. Cardiac function and remodeling were evaluated by echocardiography and heart weight index (HWI). The long-term survival of mice were analyzed. Subsequently, transcriptome sequencing was performed on myocardial tissues from the DOX group to identify key molecular alterations compared with controls. Results At the cellular level, HydroMg treatment effectively reversed DOX-induced mitochondrial dysfunction and oxidative stress, as evidenced by restored membrane potential, reductions in total ROS and mitochondrial superoxide levels by approximately 30% and 9%, respectively, and a decrease in the apoptosis rate from 34.13% to 18.27%. In the animal model, compared with the DOX group, HydroMg intervention increased left ventricular ejection fraction (LVEF) and fractional shortening (LVFS) by 9.62% and 5.82%, respectively, attenuated the reduction in HWI (4.41 mg/mm vs 3.53 mg/mm), and improved the 4-week survival rate (80% vs 60%). Transcriptomic analysis revealed that the core molecular features of DOX-induced cardiotoxicity, including widespread suppression of oxidative phosphorylation and antioxidant pathways. Conclusions HydroMg protects against DOX-induced chronic cardiotoxicity by alleviating oxidative stress and improving mitochondrial function, and provides a potential therapeutic strategy against DOX-related cardiotoxicity.
