TY - JOUR
T1 - Metabolic profiling to identify potential serum biomarkers for gastric ulceration induced by nonsteroid anti-inflammatory drugs
AU - Takeuchi, Kenichiro
AU - Ohishi, Maki
AU - Ota, Sana
AU - Suzumura, Kenichi
AU - Naraoka, Hitoshi
AU - Ohata, Takeji
AU - Seki, Jiro
AU - Miyamae, Youichi
AU - Honma, Masashi
AU - Soga, Tomoyoshi
N1 - Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2013/3
Y1 - 2013/3
N2 - Nonsteroid anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed drugs currently available. The most frequently reported serious side effects associated with NSAIDs are gastric mucosal ulceration and gastric hemorrhage. Presently, these side effects are only detectable by endoscopy, however, and no biomarkers have yet been identified. The ability to identify serum biomarkers would likely improve the safety of NSAID use. In this study we performed capillary electrophoresis-mass spectrometry (CE-MS)-based metabolomic profiling in stomach extract and serum from rats administered NSAIDs. Results showed drug-induced decreases in levels of citrate, cis-aconitate, succinate, 3-hydroxy butanoic acid, o-acetyl carnitine, proline, and hydroxyproline. We consider that these changes are due to NSAID-induced depression of mitochondrial function and activation of collagenase by lesions in the stomach. In addition, four of these changes in metabolite levels in the stomach were significantly correlated with changes in the serum. While further study is needed to clarify the mechanism of change in the level of these biomarkers, limitation of indications, and extrapolation to humans, these new serum biomarker candidates of gastric injury may be useful in the monitoring of NSAID-induced tissue damage.
AB - Nonsteroid anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed drugs currently available. The most frequently reported serious side effects associated with NSAIDs are gastric mucosal ulceration and gastric hemorrhage. Presently, these side effects are only detectable by endoscopy, however, and no biomarkers have yet been identified. The ability to identify serum biomarkers would likely improve the safety of NSAID use. In this study we performed capillary electrophoresis-mass spectrometry (CE-MS)-based metabolomic profiling in stomach extract and serum from rats administered NSAIDs. Results showed drug-induced decreases in levels of citrate, cis-aconitate, succinate, 3-hydroxy butanoic acid, o-acetyl carnitine, proline, and hydroxyproline. We consider that these changes are due to NSAID-induced depression of mitochondrial function and activation of collagenase by lesions in the stomach. In addition, four of these changes in metabolite levels in the stomach were significantly correlated with changes in the serum. While further study is needed to clarify the mechanism of change in the level of these biomarkers, limitation of indications, and extrapolation to humans, these new serum biomarker candidates of gastric injury may be useful in the monitoring of NSAID-induced tissue damage.
KW - capillary electrophoresis-mass spectrometry
KW - diagnostic marker candidate
KW - gastric injury
KW - metabolomics
KW - nonsteroid anti-inflammatory drugs
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U2 - 10.1021/pr3010452
DO - 10.1021/pr3010452
M3 - Article
C2 - 23336624
AN - SCOPUS:84874634612
SN - 1535-3893
VL - 12
SP - 1399
EP - 1407
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 3
ER -