Metabolomics profiling of doxorubicin-induced cardiotoxicity in mice with lung injury
10.11665/j.issn.1000-5048.20221218001
- VernacularTitle:阿霉素致肺损伤小鼠心脏毒性的代谢组学研究
- Author:
Jing WU
1
;
Xinyue YU
;
Yan XU
;
Yin HUANG
;
Yuxin ZHANG
Author Information
1. 中国药科大学南京鼓楼医院
- Publication Type:Journal Article
- Keywords:
cardio-oncology;
lung injury;
chemotherapy;
metabolomics;
mass spectrometry
- From:
Journal of China Pharmaceutical University
2023;54(2):198-207
- CountryChina
- Language:Chinese
-
Abstract:
Cardiotoxicity of cancer chemotherapeutics has received considerable attention in recent years.However, the effects of chemotherapy on cardiometabolic perturbation with lung injury have rarely been reported. Thus, we constructed a mouse model of myocardial injury superimposed on lung injury with a combination of bleomycin (BLM) and doxorubicin (DOX).C57BL/6J mice were randomly divided into four groups: control group (CON), BLM group (intratracheal infusion with single doses of 5 mg/kg), DOX group (intraperitoneal injection of 7.5 mg/kg/week, two weeks) and DOX+BLM group. The cardiac injury of mice was evaluated by serum biochemical parameters and histopathology.Cardiometabolic perturbation was investigated using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography with tandem mass spectrometry (LC-MS).The results showed that, compared with the CON group, BLM alone caused lung injury yet with no significant effects on the cardiometabolic profile; DOX alone had significant perturbations in the cardiometabolic profile, and the main differential metabolites were amino acids, fatty acids, phospholipids, etc.; the combination of BLM and DOX caused more severe disturbance of cardiometabolic homeostasis in mice, especially accumulation of branched-chain amino acids.This study confirmed that DOX can lead to more significant changes in the cardiometabolic profile in the presence of lung injury, with an initial focus on the branched-chain amino acid metabolic pathway.This research provides scientific data for in-depth study of the cardiotoxicity mechanism of chemotherapeutic agents.
