Potential urinary biomarkers of nephrotoxicity in cyclophosphamide-treated rats investigated by NMR-based metabolic profiling

Sa Rang Lim, Sun Hee Hyun, Seul Gi Lee, Jin Young Kim, So Hyun Kim, Sang Jin Park, Kyoung Sik Moon, Dong Geun Sul, Dong Hyun Kim, Hyung Kyoon Choi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The anticancer-drug cyclophosphamide (CP) is known to have nephrotoxicity. The aim of this study was to identify urinary biomarkers indicating CP-induced nephrotoxicity. We investigated the urine metabolic profiles using nuclear magnetic resonance spectrometry of rats administered with single high-doses of CP (0, 30, and 100 mg/kg body weight) and daily low-doses over a 4-week period (0, 1, 3, and 10 mg/kg body weight). Among 18 identified urinary metabolites, 2-oxoglutarate, citrate, hippurate, formate, valine, and alanine for short-term and 2-oxoglutarate, citrate, hippurate, isoleucine, leucine, allantoin, valine, and lysine for long-term were selected as potential biomarkers. Pathway-enrichment analysis suggested that the urinary metabolism of CP is related to valine, leucine, and isoleucine biosynthesis; taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; citrate cycle; and alanine, aspartate, and glutamate metabolism, with high pathway impact. The potential biomarkers obtained in this study could be used to monitor CP-induced nephrotoxicity relative to dose and treatment time.

Original languageEnglish
Article numbere21871
JournalJournal of Biochemical and Molecular Toxicology
Volume31
Issue number3
DOIs
Publication statusPublished - 2017 Mar 1

Keywords

  • H-NMR
  • Cyclophosphamide
  • Metabolic profiling
  • Nephrotoxicity
  • Urine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Toxicology
  • Health, Toxicology and Mutagenesis

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