Potential urinary biomarkers of nephrotoxicity in cyclophosphamide-treated rats investigated by NMR-based metabolic profiling
- Authors
- Lim, Sa Rang; Hyun, Sun-Hee; Lee, Seul Gi; Kim, Jin-Young; Kim, So-Hyun; Park, Sang-Jin; Moon, Kyoung-Sik; Sul, Donggeun; Kim, Dong Hyun; Choi, Hyung-Kyoon
- Issue Date
- Mar-2017
- Publisher
- WILEY
- Keywords
- Cyclophosphamide; H-1-NMR; Metabolic profiling; Nephrotoxicity; Urine
- Citation
- JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, v.31, no.3
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
- Volume
- 31
- Number
- 3
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/84362
- DOI
- 10.1002/jbt.21871
- ISSN
- 1095-6670
1099-0461
- 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.
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