Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats |
| |
Authors: | So Young Um Jung Hyun Park Myeon Woo Chung Kyu-Bong Kim Seon Hwa Kim Ki Hwan Choi Hwa Jeong Lee |
| |
Institution: | 1. Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk, South Korea;2. Division of Life and Pharmaceutical Science & College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul, South Korea;3. College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam, South Korea |
| |
Abstract: | 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 5 h after oral administration of indomethacin (25 mg kg−1) or co-administration with cimetidine (100 mg kg−1), which protects against GI damage. The 1H-NMR urine spectra were divided into spectral bins (0.04 ppm) 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 (10 mg kg−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. |
| |
Keywords: | Metabolomics Indomethacin Cimetidine· Gastric damage NMR Biomarker |
本文献已被 ScienceDirect 等数据库收录! |
|