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已发表论文
整合代谢组学和离子组学鉴定出小鼠顺铂治疗相关的器官特异性反应
Authors Sun R, Xiao Q, Long H, Dang R, Zhao S, Guo J , Chu X, Sun H, Zhang Y, Jiang P
Received 22 April 2025
Accepted for publication 10 September 2025
Published 22 September 2025 Volume 2025:19 Pages 8613—8639
DOI https://doi.org/10.2147/DDDT.S531720
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Anastasios Lymperopoulos
Rong Sun,1,* Qin Xiao,2,* Houlong Long,1 Ruili Dang,3,4 Shiyuan Zhao,3,4 Jinxiu Guo,3,4 Xue Chu,3,4 Haosen Sun,5 Yazhou Zhang,6 Pei Jiang3,4
1Department of Thyroid and Breast Surgery, Tengzhou Central People’s Hospital, Xuzhou Medical University, Tengzhou, 277500, People’s Republic of China; 2Department of Burn and Wound Repair Surgery, Tengzhou Central People’s Hospital, Xuzhou Medical University, Tengzhou, 277500, People’s Republic of China; 3Institute of Translational Pharmacy, Jining Medical Research Academy, Jining, 272000, People’s Republic of China; 4Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Shandong First Medical University, Jining, 272000, People’s Republic of China; 5Financial Management, Grade 2023, Panhe Campus, Shandong Agricultural University, Taian, 271000, People’s Republic of China; 6Department of Foot and Ankle Surgery, Tengzhou Central People’s Hospital,Xuzhou Medical University, Tengzhou, 277500, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yazhou Zhang, Department of Foot and Ankle Surgery, Tengzhou Central People’s Hospital, Xuzhou Medical University, Tengzhou, 277500, People’s Republic of China, Email jiangnanasia@126.com Pei Jiang, Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Shandong First Medical University, Jining, 272000, People’s Republic of China, Email jiangpeicsu@sina.com
Background: Cisplatin is a widely used chemotherapeutic agent effective against various malignant tumors. However, its clinical application is limited by severe toxic side effects on multiple vital organs. Understanding the systemic metabolic and elemental alterations associated with cisplatin is essential for developing strategies to mitigate its toxicity.
Methods: An integrative metabolomics and ionomics approach was employed to investigate organ-specific responses to cisplatin treatment in mice. Gas chromatography-mass spectrometry (GC-MS) and inductively coupled plasma-mass spectrometry (ICP-MS) were used to analyze metabolic and elemental changes in multiple organs, including the heart, liver, spleen, lungs, kidneys, cortex, hippocampus, brown adipose tissue, and blood. Histopathological evaluation was also performed to complement biochemical analyses.
Results: Multivariate statistical analysis indicated that cisplatin was accompanied by significant changes in the levels of several key metabolites, including amino acids, fatty acids, and tricarboxylic acid cycle intermediates. A total of 9 metabolic pathways were implicated, particularly those involved in amino acid biosynthesis, energy metabolism, and redox regulation. In parallel, notable variations in metal ion concentrations, such as Ag, Na, Ca, Zn, Cu, Mg and Fe, were observed across organs. These changes may be linked to alterations in enzyme activity and antioxidant functions.
Conclusion: This study provides a comprehensive overview of metabolic and elemental disturbances in vital organs correlated with cisplatin exposure. The findings suggest that modulation of specific metabolites and trace elements may help reduce cisplatin toxicity. The integrative omics approach offers novel insights into the pathways potentially underlying chemotherapy-induced side effects and highlights possible therapeutic targets.
Keywords: metabolomics, ionomics, cisplatin, organ toxicity
1Department of Thyroid and Breast Surgery, Tengzhou Central People’s Hospital, Xuzhou Medical University, Tengzhou, 277500, People’s Republic of China; 2Department of Burn and Wound Repair Surgery, Tengzhou Central People’s Hospital, Xuzhou Medical University, Tengzhou, 277500, People’s Republic of China; 3Institute of Translational Pharmacy, Jining Medical Research Academy, Jining, 272000, People’s Republic of China; 4Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Shandong First Medical University, Jining, 272000, People’s Republic of China; 5Financial Management, Grade 2023, Panhe Campus, Shandong Agricultural University, Taian, 271000, People’s Republic of China; 6Department of Foot and Ankle Surgery, Tengzhou Central People’s Hospital,Xuzhou Medical University, Tengzhou, 277500, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yazhou Zhang, Department of Foot and Ankle Surgery, Tengzhou Central People’s Hospital, Xuzhou Medical University, Tengzhou, 277500, People’s Republic of China, Email jiangnanasia@126.com Pei Jiang, Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Shandong First Medical University, Jining, 272000, People’s Republic of China, Email jiangpeicsu@sina.com
Background: Cisplatin is a widely used chemotherapeutic agent effective against various malignant tumors. However, its clinical application is limited by severe toxic side effects on multiple vital organs. Understanding the systemic metabolic and elemental alterations associated with cisplatin is essential for developing strategies to mitigate its toxicity.
Methods: An integrative metabolomics and ionomics approach was employed to investigate organ-specific responses to cisplatin treatment in mice. Gas chromatography-mass spectrometry (GC-MS) and inductively coupled plasma-mass spectrometry (ICP-MS) were used to analyze metabolic and elemental changes in multiple organs, including the heart, liver, spleen, lungs, kidneys, cortex, hippocampus, brown adipose tissue, and blood. Histopathological evaluation was also performed to complement biochemical analyses.
Results: Multivariate statistical analysis indicated that cisplatin was accompanied by significant changes in the levels of several key metabolites, including amino acids, fatty acids, and tricarboxylic acid cycle intermediates. A total of 9 metabolic pathways were implicated, particularly those involved in amino acid biosynthesis, energy metabolism, and redox regulation. In parallel, notable variations in metal ion concentrations, such as Ag, Na, Ca, Zn, Cu, Mg and Fe, were observed across organs. These changes may be linked to alterations in enzyme activity and antioxidant functions.
Conclusion: This study provides a comprehensive overview of metabolic and elemental disturbances in vital organs correlated with cisplatin exposure. The findings suggest that modulation of specific metabolites and trace elements may help reduce cisplatin toxicity. The integrative omics approach offers novel insights into the pathways potentially underlying chemotherapy-induced side effects and highlights possible therapeutic targets.
Keywords: metabolomics, ionomics, cisplatin, organ toxicity