NMR based metabolomic approach revealed cyclophosphamide-induced systematic alterations in a rat model

Abstract

Cyclophosphamide (CY) is the most commonly used antineoplastic drug, but various side effects are often observed. In this work, a ¹H NMR based metabolomic approach combined with biochemical assay and histopathological inspection were employed to study the toxic effects of CY on rats. The endogenous metabolites in liver, kidney, and heart were identified. Multivariate analysis revealed that the 18 metabolites in the liver, 14 metabolites in the kidney, and 6 metabolites in the heart were significantly altered after CY treatment. Metabolic pathway analysis showed that the metabolic alterations were related to amino acids metabolism, energy metabolism, choline metabolism, nucleotide metabolism and oxidative stress-related metabolism. This integrative study should be useful for the clinical safety evaluation of CY, and shows the power of a ¹H NMR-based metabolomic approach to evaluate the toxicity of drugs systematically.