Metabolomic analysis to discover candidate therapeutic agents against acute pancreatitis

Aya Sakai, Shin Nishiumi, Yuuki Shiomi, Takashi Kobayashi, Yoshihiro Izumi, Hiromu Kutsumi, Takanobu Hayakumo, Takeshi Azuma, Masaru Yoshida

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Novel and effective drugs against acute pancreatitis are required. Therefore, we examined the changes in the metabolite levels in the serum and pancreatic tissue of mice with cerulein- and arginine-induced pancreatitis using gas-chromatography/mass-spectrometry (GC/MS) and investigated whether these alterations affected the severity of acute pancreatitis. In the cerulein-induced pancreatitis model, 93 and 129 metabolites were detected in the serum and pancreatic tissue, respectively. In the l-arginine-induced acute pancreatitis model, 120 and 133 metabolites were detected in the serum and pancreatic tissue, respectively. Among the metabolites, the concentrations of tricarboxylic acid (TCA) cycle intermediates and amino acids were altered in pancreatitis, and in pancreatic tissue, the levels of the intermediates involved in the initial part of the TCA cycle were increased and those of the intermediates involved in the latter part of the TCA cycle were decreased. Some metabolites exhibited similar changes in both pancreatitis mouse models, e.g., the levels of glutamic acid and O-phosphoethanolamine were significantly decreased in the pancreatic tissue. Supplementation with glutamic acid and O-phosphoethanolamine attenuated the severity of cerulein-induced acute pancreatitis. Our results suggest that GC/MS-based metabolomics is capable of accurately representing the status of acute pancreatitis, leading to the discovery of therapeutic agents for pancreatitis.

Original languageEnglish
Pages (from-to)107-120
Number of pages14
JournalArchives of Biochemistry and Biophysics
Volume522
Issue number2
DOIs
Publication statusPublished - Jun 15 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

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  • Cite this

    Sakai, A., Nishiumi, S., Shiomi, Y., Kobayashi, T., Izumi, Y., Kutsumi, H., Hayakumo, T., Azuma, T., & Yoshida, M. (2012). Metabolomic analysis to discover candidate therapeutic agents against acute pancreatitis. Archives of Biochemistry and Biophysics, 522(2), 107-120. https://doi.org/10.1016/j.abb.2012.03.025