Metabonomics study on nephrotoxicity induced by intraperitoneal and intravenous cisplatin administration using rapid resolution liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (RRLC-Q-TOF-MS)

Abstract

Cisplatin is a well-known chemotherapeutic agent in cancer therapy. It is commonly administered intraperitoneally and intravenously in the clinic. The use of cisplatin is limited by its side effects, particularly its nephrotoxicity. In this study, mass spectrometry-based metabonomics coupled with multivariate statistical analysis was used to find biomarkers of kidney injury and further applied to investigate on the disturbed metabolic pathways, which were induced by single intraperitoneal or intravenous injection of cisplatin to rats with the dosage of 6 mg kg⁻¹. It was found that sixteen biomarkers were changed because of drug administration. Among these sixteen biomarkers, eight biomarkers, including LPC(20:3), creatinine, LPC(14:0), LPC(18:3), LPC(22:5), arachidonic acid, proline and tryptophan, were found to be related to biochemical indicators of nephrotoxicity using Pearson correlation analysis. The identified biomarkers were mainly involved in valine, leucine and isoleucine biosynthesis, metabolism of sphingolipid, arginine and proline, glycerophospholipid, tryptophan, and arachidonic acid. In addition, the disturbed pathways were found to be time- and intraperitoneal or intravenous administration-dependent. The present result shows that mass spectrometry-based metabonomics approaches could be applied to study changes in metabolites and metabolic pathways associated with intraperitoneal or intravenous injection of cisplatin.