Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

• Published in: Analytica chimica acta Vol. 722; pp. 87 - 94
• Main Authors: Um, So Young, Park, Jung Hyun, Chung, Myeon Woo, Kim, Kyu-Bong, Kim, Seon Hwa, Choi, Ki Hwan, Lee, Hwa Jeong
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 13.04.2012; Elsevier
• Subjects: Analytical chemistry; Animals; Anti-Inflammatory Agents, Non-Steroidal - metabolism; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biomarker; Chemistry; Cimetidine· Gastric damage; Discriminant Analysis; Exact sciences and technology; Gastric Mucosa - drug effects; Indomethacin; Indomethacin - metabolism; Indomethacin - pharmacology; Least-Squares Analysis; Magnetic Resonance Spectroscopy; Male; Metabolomics; NMR; Principal Component Analysis; Rats; Rats, Sprague-Dawley; Spectrometric and optical methods; Metabolomics; NMR; Biomarker; Indomethacin; Cimetidine· Gastric damage; Drug; Urine; Data analysis; Rat; Metabolite; Rodentia; Prediction; Biological marker; NMR spectrometry; Acetate; Pattern recognition; Multivariate analysis; PLS regression; Vertebrata; Target; Mammalia; Endogenous; Cimetidine Gastric damage; Animal; Pattern analysis
• ISSN: 0003-2670; 1873-4324
• DOI: 10.1016/j.aca.2012.01.062

. [Display omitted] ► NMR based metabolomics – gastric damage by indomethacin. ► Pattern recognition analysis was performed to biomarkers of gastric damage. ► 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. ► The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the 1H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5h after oral administration of indomethacin (25mgkg−1) or co-administration with cimetidine (100mgkg−1), which protects against GI damage. The 1H-NMR urine spectra were divided into spectral bins (0.04ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10mgkg−1) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by NSAIDs can be screened in the preclinical stage of drug development using a NMR based metabolomics approach.