Toxicity analysis of doxorubicin using plasma metabolomics technology based on rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry

Analytical Methods

Haoyue Deng²  Simiao Fan²  Lei Wang²  Zhenzhu Zhang²  Huifang Zhou¹  Xiuxiu Zhang²  Yanjun Zhang²  Yuming Wang²  Yubo Li² 

[1] Department of Experimental Teaching, Tianjin University of Traditional Chinese Medicine, 88 Yuquan Road,Tianjin 300193,ChinaDepartment of Experimental Teaching, Tianjin University of Traditional Chinese Medicine, 88 Yuquan Road,Tianjin 300193,ChinaDepartment of Experimental Teaching, Tianjin University of Traditional Chinese Medicine, 88 Yuquan Road,Tianjin 300193,China;Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan west Road,Tianjin 300193,ChinaTianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan west Road,Tianjin 300193,ChinaTianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan west Road,Tianjin 300193,China

DOI  :  10.1039/C4AY00762J

学科分类：分析化学

来源: Royal Society of Chemistry

【 摘 要 】

Doxorubicin is a highly efficient antitumor drug, but it can induce toxicity, largely affecting people's life. Metabolomics technology, a part of systems biology, can offer information on the changes in metabolic profiles of biofluids upon drug administration. Meanwhile, the study of plasma metabolomics of doxorubicin toxicity using liquid chromatography-mass spectrometry technology is not very clear. In this study, a plasma metabolomics approach using rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry technology was used to investigate the toxic mechanism of doxorubicin from a metabolic view. The biochemical analysis and histopathological examination results showed that a toxicity model can be built by intraperitoneal injection of doxorubicin with a dose of 15 mg kg−1 in male Wistar rats. Metabolomics results revealed that fifteen biomarkers were changed due to doxorubicin-induced toxicity. Besides, arachidonic acid metabolism, valine, leucine and isoleucine biosynthesis, sphingolipid metabolism, glycerophospholipid metabolism and primary bile acid biosynthesis were mainly responsible for the toxicity of doxorubicin. The changed metabolites and interrupted pathways found in this study are meaningful and the results can lay the foundation for further research on the toxicity mechanism of doxorubicin.

【 授权许可】

Unknown