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.
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.
Bailón
Elvira
E
Department of Pharmacology, CIBER-EHD, School of Pharmacy, University of Granada, Spain.
Comalada
Mònica
M
Román
Juan
J
Michelena
Pedro
P
Ramis
Isabel
I
Merlos
Manuel
M
Nieto
Ana
A
Concha
Angel
A
Zarzuelo
Antonio
A
Gálvez
Julio
J
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
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