title: Metabolomic analysis to discover candidate therapeutic agents against acute pancreatitis.
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.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Sakai
authors.forename: Shin
authors.initials: S
authors.lastname: Nishiumi
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Shiomi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Izumi
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kutsumi
authors.forename: Takanobu
authors.initials: T
authors.lastname: Hayakumo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000208:Acute Disease; D000596:Amino Acids / Q000097:blood; D000818:Animals; D001120:Arginine / Q000633:toxicity; D002108:Ceruletide / Q000633:toxicity; D002952:Citric Acid Cycle; D004195:Disease Models, Animal; D004983:Ethanolamines / Q000627:therapeutic use; D008401:Gas Chromatography-Mass Spectrometry; D018698:Glutamic Acid / Q000627:therapeutic use; D008297:Male; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D004983:Ethanolamines; D018698:Glutamic Acid; C005448:phosphorylethanolamine; D002108:Ceruletide; D001120:Arginine