title: Uric acid ameliorates indomethacin-induced enteropathy in mice through its antioxidant activity.
abstract: OBJECTIVE
  Uric acid is excreted from blood into the intestinal lumen, yet the roles of uric acid in intestinal diseases remain to be elucidated. The study aimed to determine whether uric acid could reduce end points associated with nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy.
  
  
  METHODS
  A mouse model of NSAID-induced enteropathy was generated by administering indomethacin intraperitoneally to 8-week-old male C57BL/6 mice, and then vehicle or uric acid was administered orally. A group of mice treated with indomethacin was also concurrently administered inosinic acid, a uric acid precursor, and potassium oxonate, an inhibitor of uric acid metabolism, intraperitoneally. For in vitro analysis, Caco-2 cells treated with indomethacin were incubated in the presence or absence of uric acid.
  
  
  RESULTS
  Oral administration of uric acid ameliorated NSAID-induced enteropathy in mice even though serum uric acid levels did not increase. Intraperitoneal administration of inosinic acid and potassium oxonate significantly elevated serum uric acid levels and ameliorated NSAID-induced enteropathy in mice. Both oral uric acid treatment and intraperitoneal treatment with inosinic acid and potassium oxonate significantly decreased lipid peroxidation in the ileum of mice with NSAID-induced enteropathy. Treatment with uric acid protected Caco-2 cells from indomethacin-induced oxidative stress, lipid peroxidation, and cytotoxicity.
  
  
  CONCLUSIONS
  Uric acid within the intestinal lumen and in serum had a protective effect against NSAID-induced enteropathy in mice, through its antioxidant activity. Uric acid could be a promising therapeutic target for NSAID-induced enteropathy.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yasutake
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Tomita
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Higashiyama
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Furuhashi
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Shirakabe
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takajo
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Maruta
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Sato
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Narimatsu
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshikawa
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Kurihara
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Watanabe
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Komoto
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nagao
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Miura
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College, Tokorozawa-shi, Saitama, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Hokari
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D018938:Caco-2 Cells; D004195:Disease Models, Animal; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007213:Indomethacin / Q000009:adverse effects*; D007291:Inosine Monophosphate / Q000008:administration & dosage / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D010094:Oxonic Acid / Q000008:administration & dosage / Q000494:pharmacology; D014527:Uric Acid / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007291:Inosine Monophosphate; D014527:Uric Acid; C489337:potassium oxonate; D010094:Oxonic Acid; D007213:Indomethacin
keywords: lipid peroxidation; nonsteroidal anti-inflammatory drug-induced enteropathy; reactive oxygen species; uric acid