Metabolic profiling to identify potential serum biomarkers for gastric ulceration induced by nonsteroid anti-inflammatory drugs

Kenichiro Takeuchi, Maki Ohishi, Sana Ota, Kenichi Suzumura, Hitoshi Naraoka, Takeji Ohata, Jiro Seki, Youichi Miyamae, Masashi Honma, Tomoyoshi Soga

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1399-1407
Number of pages9
JournalJournal of Proteome Research
Volume12
Issue number3
DOIs
Publication statusPublished - 2013

Fingerprint

Biomarkers
Stomach
Anti-Inflammatory Agents
Serum
Pharmaceutical Preparations
Aconitic Acid
Acetylcarnitine
Gastrointestinal Agents
Capillary electrophoresis
Metabolomics
Endoscopy
3-Hydroxybutyric Acid
Hydroxyproline
Capillary Electrophoresis
Succinic Acid
Collagenases
Metabolites
Proline
Extrapolation
Citric Acid

Keywords

  • capillary electrophoresis-mass spectrometry
  • diagnostic marker candidate
  • gastric injury
  • metabolomics
  • nonsteroid anti-inflammatory drugs

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Metabolic profiling to identify potential serum biomarkers for gastric ulceration induced by nonsteroid anti-inflammatory drugs. / Takeuchi, Kenichiro; Ohishi, Maki; Ota, Sana; Suzumura, Kenichi; Naraoka, Hitoshi; Ohata, Takeji; Seki, Jiro; Miyamae, Youichi; Honma, Masashi; Soga, Tomoyoshi.

In: Journal of Proteome Research, Vol. 12, No. 3, 2013, p. 1399-1407.

Research output: Contribution to journalArticle

Takeuchi, K, Ohishi, M, Ota, S, Suzumura, K, Naraoka, H, Ohata, T, Seki, J, Miyamae, Y, Honma, M & Soga, T 2013, 'Metabolic profiling to identify potential serum biomarkers for gastric ulceration induced by nonsteroid anti-inflammatory drugs', Journal of Proteome Research, vol. 12, no. 3, pp. 1399-1407. https://doi.org/10.1021/pr3010452
Takeuchi, Kenichiro ; Ohishi, Maki ; Ota, Sana ; Suzumura, Kenichi ; Naraoka, Hitoshi ; Ohata, Takeji ; Seki, Jiro ; Miyamae, Youichi ; Honma, Masashi ; Soga, Tomoyoshi. / Metabolic profiling to identify potential serum biomarkers for gastric ulceration induced by nonsteroid anti-inflammatory drugs. In: Journal of Proteome Research. 2013 ; Vol. 12, No. 3. pp. 1399-1407.
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