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

Abstract

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.