論文 - 詳細
| RRC ID | 62114 |
|---|---|
| 著者 | Yasutake Y, Tomita K, Higashiyama M, Furuhashi H, Shirakabe K, Takajo T, Maruta K, Sato H, Narimatsu K, Yoshikawa K, Okada Y, Kurihara C, Watanabe C, Komoto S, Nagao S, Matsuo H, Miura S, Hokari R. |
| タイトル | Uric acid ameliorates indomethacin-induced enteropathy in mice through its antioxidant activity. |
| ジャーナル | J Gastroenterol Hepatol |
| Abstract |
BACKGROUND AND AIM: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. |
| 巻・号 | 32(11) |
| ページ | 1839-1845 |
| 公開日 | 2017-11-1 |
| DOI | 10.1111/jgh.13785 |
| PMID | 28295549 |
| MeSH | Administration, Oral Animals Anti-Inflammatory Agents, Non-Steroidal / adverse effects* Caco-2 Cells Disease Models, Animal Gastrointestinal Diseases / chemically induced* Gastrointestinal Diseases / metabolism Gastrointestinal Diseases / prevention & control* Humans Ileum / metabolism Indomethacin / adverse effects* Inosine Monophosphate / administration & dosage Inosine Monophosphate / pharmacology Lipid Peroxidation / drug effects Male Mice, Inbred C57BL Oxonic Acid / administration & dosage Oxonic Acid / pharmacology Uric Acid / administration & dosage Uric Acid / blood Uric Acid / pharmacology* |
| IF | 3.437 |
| リソース情報 | |
| ヒト・動物細胞 | CACO-2(RCB0988) |