Plasma metabolic profiling analysis of neurotoxicity induced by oxaliplatin using metabonomics and multivariate data analysis

Abstract

Oxaliplatin is a third generation antitumor agent, which is often used in treating advanced colorectal cancer, but the use of oxaliplatin is limited by its side effects, especially peripheral nerve toxicity. Metabonomics techniques, as a holistic analytical technique, could provide basic information on the metabolic profile of biological fluids during drug administration. In this study, we used the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technique to analyze rat plasma samples collected seven days after oxaliplatin administration. The changes of metabolites in plasma samples were evaluated by principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), and 15 kinds of neurotoxicity-related biomarkers were screened. The metabolic pathways of interference involved amino acid biosynthesis and metabolism, glycerophospholipid metabolism, sphingolipid metabolism and so on. The biomarkers found in this study are significant for the study of neurotoxicity.