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H-1-Nuclear magnetic resonance-based metabolic profiling of nonsteroidal anti-inflammatory drug-induced adverse effects in rats

Title
H-1-Nuclear magnetic resonance-based metabolic profiling of nonsteroidal anti-inflammatory drug-induced adverse effects in rats
Authors
Um, So YoungPark, Jung HyunChung, Myeon WooChoi, Ki HwanLee, Hwa Jeong
Ewha Authors
이화정
SCOPUS Author ID
이화정scopus
Issue Date
2016
Journal Title
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
ISSN
0731-7085JCR Link1873-264XJCR Link
Citation
vol. 129, pp. 492 - 501
Keywords
Nonsteroidal anti-inflammatory drugsH-1-Nuclear magnetic resonanceGastrointestinal damagePartial least square-discrimination analysisMetabolomicsBiomarker
Publisher
ELSEVIER SCIENCE BV
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs), which are globally prescribed, exhibit mainly antiinflammatory and analgesic effects but also can cause adverse effects including gastrointestinal erosions, ulceration, bleeding, and perforation. The purpose of this study was to investigate surrogate biomarkers associated with the gastrointestinal (GI) damage caused by NSAID treatment using pattern recognition analysis of H-1-nuclear magnetic resonance (H-1 NMR) spectra of rat urine. Urine was collected for 5 h after oral administration of the following NSAIDs at low or high doses: acetylsalicylic acid (10 or 200 mg kg(-1)), diclofenac (0.5 or 15 mg kg(-1)), piroxicam (1 or 10 mg kg(-1)), indomethacin (I or 25 mg kg(-1)), or ibuprofen (10, or 150 mg kg(-1)) as nonselective COX inhibitors and celecoxib (10 or 100 mg kg(-1)) as a COX-2 selective inhibitor. The urine was analyzed using 500 MHz H-1 NMR for spectral binning and targeted profiling and the level of gastric damage was examined. The nonselective COX inhibitors caused severe gastric damage while no lesions were observed in the celecoxib-treated rats. The H-1 NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and a total of 44 endogenous metabolites were assigned for targeted profiling. Multivariate data analyses were performed to recognize the spectral pattern of endogenous metabolites related to NSAIDs using partial least square-discrimination analysis (PLS-DA). The H-1 NMR spectra clustered differently according to gastric damage score in global profiling. In targeted profiling, the endogenous metabolites of citrate, allantoin, 2-oxoglutarate, acetate, benzoate, glycine, and trimethylamine N-oxide were selected as putative biomarkers for gastric damage caused by NSAIDs. These putative biomarkers might be useful for predicting the risk of adverse effects caused by NSAIDs in the early stage of drug development process. (C) 2016 Elsevier B.V. All rights reserved.
DOI
10.1016/j.jpba.2016.07.045
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약학대학 > 약학과 > Journal papers
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