Metabolomics profiling of doxorubicin-induced cardiotoxicity in mice with lung injury

WU Jing; YU Xinyue; XU Yan; HUANG Yin; ZHANG Yuxin

doi:10.11665/j.issn.1000-5048.20221218001

Journal of China Pharmaceutical University > 2023 > 54(2): 198-207. > DOI: 10.11665/j.issn.1000-5048.20221218001

WU Jing, YU Xinyue, XU Yan, HUANG Yin, ZHANG Yuxin. Metabolomics profiling of doxorubicin-induced cardiotoxicity in mice with lung injury[J]. Journal of China Pharmaceutical University, 2023, 54(2): 198-207. DOI: 10.11665/j.issn.1000-5048.20221218001

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Metabolomics profiling of doxorubicin-induced cardiotoxicity in mice with lung injury

1.
China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing 210008
2.
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China

Funds: This study was supported by the Basic Research Program （Natural Science Foundation） of Jiangsu Province （No.BK20220193）

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Received Date: December 17, 2022
Revised Date: February 27, 2023

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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.
- cardio-oncology,
- lung injury,
- chemotherapy,
- metabolomics,
- mass spectrometry

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