title: Preventive effect of agaro-oligosaccharides on non-steroidal anti-inflammatory drug-induced small intestinal injury in mice.
abstract: OBJECTIVE
  Non-steroidal anti-inflammatory drugs (NSAIDs), which are commonly used in clinical medicine, cause erosion, ulcers, and bleeding in the gastrointestinal tract. No effective agent for the prevention and treatment of small intestinal injury by NSAIDs has been established. This study investigates the effects of agaro-oligosaccharides (AGOs) on NSAID-induced small intestinal injury in mice.
  
  
  METHODS
  Mice were treated with indomethacin, an NSAID, to induce intestinal injury. The respective degrees of mucosal injury of mice that received AGO and control mice were compared. Heme oxygenase-1 (HO-1) expression using quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry were measured. The expression of keratinocyte chemoattractant (KC) was measured using qRT-PCR and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  AGO administration induced HO-1 expression in mouse small intestinal mucosa. Induction was observed mainly in F4/80 positive macrophages. The increased ulcers score, myeloperoxidase activity, and KC expression by indomethacin were inhibited by AGO administration. Conversely, HO inhibitor cancelled AGO-mediated prevention of intestinal injury. In mouse peritoneal macrophages, AGOs enhanced HO-1 expression and suppressed lipopolysaccharide-induced KC expression. Furthermore, AGOs enhanced the expressions of alternatively activated macrophage markers arginase-1, mannose receptor-1, and chitinase 3-like 3.
  
  
  CONCLUSIONS
  Results suggest that oral administration of AGOs prevents NSAID-induced intestinal injury.
authors: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan; Department of Food Factor Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
authors: Yasuki
authors: Y
authors: Higashimura
authors: Yuji
authors: Y
authors: Naito
authors: Tomohisa
authors: T
authors: Takagi
authors: Yuko
authors: Y
authors: Tanimura
authors: Katsura
authors: K
authors: Mizushima
authors: Akihito
authors: A
authors: Harusato
authors: Akifumi
authors: A
authors: Fukui
authors: Hiroyuki
authors: H
authors: Yoriki
authors: Osamu
authors: O
authors: Handa
authors: Hiromu
authors: H
authors: Ohnogi
authors: Toshikazu
authors: T
authors: Yoshikawa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001119:Arginase / Q000378:metabolism; D002630:Chemotactic Factors / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007213:Indomethacin / Q000009:adverse effects*; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D015603:Keratinocytes; D037102:Lectins / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009844:Oligosaccharides / Q000008:administration & dosage* / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002630:Chemotactic Factors; D037102:Lectins; C581013:MRC1 protein, mouse; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D009195:Peroxidase; D051547:Heme Oxygenase-1; C429541:Chil3 protein, mouse; D001619:beta-N-Acetylhexosaminidases; C544448:Arg1 protein, mouse; D001119:Arginase; D007213:Indomethacin
keywords: M2 macrophage; heme oxygenase; indomethacin; interleukin-8; keratinocyte chemoattractant