title: The Syk Inhibitor Fostamatinib Decreases the Severity of Colonic Mucosal Damage in a Rodent Model of Colitis.
abstract: OBJECTIVE
  Inflammatory bowel disease is a chronic inflammatory disease of the gastrointestinal system. In some cases, current medications used for inflammatory bowel disease may not be enough for remission, creating a need for more potent and reliable medications. There is no study showing the efficacy of fostamatinib, with proven effects on some inflammatory diseases, on ulcerative colitis. In our study we planned to research the efficacy of fostamatinib, a spleen tyrosine kinase inhibitor, on acetic acid-induced colitis.
  
  
  METHODS
  The study included 28 male Sprague-Dawley rats, randomly divided into control group, fostamatinib group, colitis group and fostamatinib + colitis group, each containing seven rats. Colitis induction was performed with 4% acetic acid. Colonic inflammation was assessed with disease activity index, macroscopic and histological damage scores, colonic myeloperoxidase, malondialdehyde and superoxide dismutase activity, and tumour necrosis factor alpha [TNFα], CD3, Syk, and phospho-Syk expression.
  
  
  RESULTS
  There was a significant difference between the colitis and control groups in terms of all parameters. The disease activity index, macroscopic and microscopic damage scores, immunohistochemical TNFα, CD3, Syk, and phospho-Syk expression, and tissue myeloperoxidase activity were found to be significantly lower in the colitis + fostamatinib group compared with the colitis group. There was no significant difference between the two groups in terms of myeloperoxidase and malondialdehyde activity.
  
  
  CONCLUSIONS
  Fostamatinib reduced the inflammatory damage in the experimental colitis. This effect may be due to suppression of TNFα, T-lymphocytes, and neutrophils in colonic mucosa via suppression of Syk. Fostamatinib may be an appropriate treatment alternative for ulcerative colitis. Further clinical studies are required to support this.
authors.affiliation: Department of Gastroenterology, Abant İzzet Baysal University, Faculty of Medicine, Bolu, Turkey dr_guraycan@yahoo.com.
authors.forename: Guray
authors.initials: G
authors.lastname: Can
authors.affiliation: Department of Pediatric Surgery, Trakya University Faculty of Medicine, Edirne, Turkey.
authors.forename: Suleyman
authors.initials: S
authors.lastname: Ayvaz
authors.affiliation: Department of Internal Medicine, Abant İzzet Baysal University, Faculty of Medicine, Bolu, Turkey.
authors.forename: Hatice
authors.initials: H
authors.lastname: Can
authors.affiliation: Department of Histology and Embryology, Trakya University, Faculty of Medicine, Edirne, Turkey.
authors.forename: Selim
authors.initials: S
authors.lastname: Demirtas
authors.affiliation: Department of Biochemistry, Balıkesir University Faculty of Veterinary, Balıkesir, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Aksit
authors.affiliation: Department of Gastroenterology, Bolu İzzet Baysal State Hospital, Bolu, Turkey.
authors.forename: Bulent
authors.initials: B
authors.lastname: Yilmaz
authors.affiliation: Department of Gastroenterology, Bolu İzzet Baysal State Hospital, Bolu, Turkey.
authors.forename: Ugur
authors.initials: U
authors.lastname: Korkmaz
authors.affiliation: Department of Gastroenterology, Abant İzzet Baysal University, Faculty of Medicine, Bolu, Turkey.
authors.forename: Mevlut
authors.initials: M
authors.lastname: Kurt
authors.affiliation: Department of Histology and Embryology, Trakya University, Faculty of Medicine, Edirne, Turkey.
authors.forename: Turan
authors.initials: T
authors.lastname: Karaca
mesh_terms: D019342:Acetic Acid; D000631:Aminopyridines; D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D008297:Male; D009025:Morpholines; D010078:Oxazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000627:therapeutic use*; D011743:Pyrimidines; D051381:Rats; D017207:Rats, Sprague-Dawley; D000072377:Syk Kinase
chemical_list: D000631:Aminopyridines; D047908:Intracellular Signaling Peptides and Proteins; D009025:Morpholines; D010078:Oxazines; D011725:Pyridines; D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606898:Syk protein, rat; D019342:Acetic Acid; C523665:fostamatinib
keywords: Acetic acid-induced colitis; fostamatinib; rats; spleen tyrosine kinase