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

2 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

Fingerprint

Biomarkers
Cyclophosphamide
Rats
Metabolism
Nuclear magnetic resonance
Valine
Citric Acid
formic acid
Isoleucine
Leucine
Alanine
Body Weight
Allantoin
Metabolome
Taurine
Biosynthesis
Metabolites
Aspartic Acid
Spectrometry
Lysine

Keywords

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

ASJC Scopus subject areas

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

Cite this

Potential urinary biomarkers of nephrotoxicity in cyclophosphamide-treated rats investigated by NMR-based metabolic profiling. / Lim, Sa Rang; Hyun, Sun Hee; Lee, Seul Gi; Kim, Jin Young; Kim, So Hyun; Park, Sang Jin; Moon, Kyoung Sik; Sul, Dong Geun; Kim, Dong Hyun; Choi, Hyung Kyoon.

In: Journal of Biochemical and Molecular Toxicology, Vol. 31, No. 3, e21871, 01.03.2017.

Research output: Contribution to journalArticle

Lim, Sa Rang ; Hyun, Sun Hee ; Lee, Seul Gi ; Kim, Jin Young ; Kim, So Hyun ; Park, Sang Jin ; Moon, Kyoung Sik ; Sul, Dong Geun ; Kim, Dong Hyun ; Choi, Hyung Kyoon. / Potential urinary biomarkers of nephrotoxicity in cyclophosphamide-treated rats investigated by NMR-based metabolic profiling. In: Journal of Biochemical and Molecular Toxicology. 2017 ; Vol. 31, No. 3.
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