title: UR-1505, a salicylate able to selectively block T-cell activation, shows intestinal anti-inflammatory activity in the chronic phase of the DSS model of rat colitis.
abstract: BACKGROUND
  UR-1505 is a novel salicylate derivative compound that has been demonstrated to selectively down-regulate T-cell activation. The aim of the present study was to elucidate the mechanisms involved in the intestinal anti-inflammatory effects of UR-1505 in 2 protocols of a dextran sodium sulfate (DSS) model of rat colitis: acute and established colitis.
  
  
  METHODS
  The first protocol consisted of incorporating DSS into the drinking water at a concentration of 5% (w/v) for 5 days (acute initial colitis). In the second protocol, once the acute colitis had been induced, the concentration of DSS was reduced to 2% (w/v) and maintained for 10 days (established colitis).
  
  
  RESULTS
  The results obtained demonstrated that although UR-1505 did not exert a significant intestinal anti-inflammatory effect in ameliorating the initial steps of the intestinal inflammation induced by DSS, it had a beneficial effect on ongoing inflammation, most probably through inhibiting activation of T lymphocytes, thus avoiding perpetuation of the inflammatory process.
  
  
  CONCLUSIONS
  These results suggest that this compound is a good candidate for inducing remission or maintaining therapies in human inflammatory bowel disease (IBD). Moreover, the different results obtained by UR-1505 in these 2 protocols of colitis induction (acute initial colitis versus established colitis) confirm the importance of selection and optimization of the experimental model to evaluate the drugs to be used in IBD therapy.
authors.affiliation: Department of Pharmacology, CIBER-EHD, School of Pharmacy, University of Granada, Spain.
authors.forename: Elvira
authors.initials: E
authors.lastname: Bailón
authors.forename: Mònica
authors.initials: M
authors.lastname: Comalada
authors.forename: Juan
authors.initials: J
authors.lastname: Román
authors.forename: Pedro
authors.initials: P
authors.lastname: Michelena
authors.forename: Isabel
authors.initials: I
authors.lastname: Ramis
authors.forename: Manuel
authors.initials: M
authors.lastname: Merlos
authors.forename: Ana
authors.initials: A
authors.lastname: Nieto
authors.forename: Angel
authors.initials: A
authors.lastname: Concha
authors.forename: Antonio
authors.initials: A
authors.lastname: Zarzuelo
authors.forename: Julio
authors.initials: J
authors.lastname: Gálvez
mesh_terms: D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D016264:Dextran Sulfate; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*; D005466:Fluorocarbons
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016264:Dextran Sulfate; D012459:Salicylates; C522458:2-hydroxy-4-(2,2,3,3,3-pentafluoropropoxy)benzoic acid; D005466:Fluorocarbons