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Potential metabolomic biomarkers for evaluation of adriamycin efficacy using a urinary 1 H‐NMR spectroscopy
Author(s) -
Kim KyuBong,
Yang JiYoung,
Kwack Seung Jun,
Kim Hyung Sik,
Ryu Do Hyun,
Kim YeonJoo,
Bae Jung Yun,
Lim Duck Soo,
Choi Seul Min,
Kwon Mi Jung,
Bang Du Yeon,
Lim Seong Kwang,
Kim Young Woo,
Hwang GeumSook,
Lee ByungMu
Publication year - 2013
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2778
Subject(s) - trigonelline , taurine , chemistry , trimethylamine , metabolomics , trimethylamine n oxide , pharmacology , metabolome , carnitine , medicine , biochemistry , chromatography , amino acid
A metabolomics approach using proton nuclear magnetic resonance (NMR) was applied to investigate metabolic alterations following adriamycin (ADR) treatment for gastric adenocarcinoma. After BALB/c‐nu/nu mice were implanted with human gastric adenocarcinoma, ADR (1 or 3 mg kg −1 per day) was intraperitoneally administered for 5 days. Urine was collected on days 2 and 5 and analyzed by NMR. The levels of trimethylamine oxide (TMAO, ×0.3), hippurate (×0.3) and taurine (×0.6) decreased significantly ( P < 0.05), whereas the levels of 3‐indoxylsulfate (×12.6), trigonelline (×1.5), citrate (×2.5), trimethylamine (TMA, ×2.0) and 2‐oxoglutarate (×2.3) increased significantly ( P < 0.05) in the tumor model. After ADR treatment, TMAO, hippuarte and taurine were increased significantly on day 5 compared with those of the tumor model. The levels of 2‐oxoglutarate, 3‐indoxylsulfate, trigonelline, TMA and citrate, which increased in the tumor model, significantly decreased to those of normal control by ADR treatment. Furthermore, the ratio between TMA and TMAO was dramatically altered in both tumor and ADR‐treated groups. Overall, metabolites such as TMAO, TMA, 3‐indoxylsulfate, hippurate, trigonelline, citrate and 2‐oxoglutarate related to the tricarboxylic acid (TCA) cycle might be considered as therapeutic targets to potentiate the efficacy of ADR. Thus, these results suggest that the metabolomics analysis of tumor response to ADR treatment may be applicable for demonstrating the efficacy of anticancer agent, ADR and treatment adaptation. Copyright © 2012 John Wiley & Sons, Ltd.