title: Metabolic profiling to identify potential serum biomarkers for gastric ulceration induced by nonsteroid anti-inflammatory drugs.
abstract: 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.
authors: Drug Safety Research Laboratories, Astellas Pharma Inc, 1-6 Kashima 2-chome, Yodogawa-ku, Osaka 532-8514, Japan.
authors: Kenichiro
authors: K
authors: Takeuchi
authors: Maki
authors: M
authors: Ohishi
authors: Sana
authors: S
authors: Ota
authors: Kenichi
authors: K
authors: Suzumura
authors: Hitoshi
authors: H
authors: Naraoka
authors: Takeji
authors: T
authors: Ohata
authors: Jiro
authors: J
authors: Seki
authors: Youichi
authors: Y
authors: Miyamae
authors: Masashi
authors: M
authors: Honma
authors: Tomoyoshi
authors: T
authors: Soga
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood*; D019075:Electrophoresis, Capillary; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000097:blood* / Q000139:chemically induced
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers