Potential urinary biomarkers of nephrotoxicity in cyclophosphamide‐treated rats investigated by NMR‐based metabolic profiling. Issue 3 (21st November 2016)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of biochemical and molecular toxicology. Volume 31:Issue 3(2017)
• Page Start: N/A
• Page End: N/A
• Publication Date: 2016-11-21
• Subjects: Cyclophosphamide -- 1H‐NMR -- Metabolic profiling -- Nephrotoxicity -- Urine; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Toxicology -- Periodicals; 574
• DOI: 10.1002/jbt.21871
• Languages: English
• ISSNs: 1095-6670

Abstract

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.