Effects of the gastrin-releasing peptide antagonist RC-3095 in a rat model of ulcerative colitis.
BACKGROUND
RC-3095, a synthetic gastrin-releasing peptide (GRP) antagonist, has been identified as a candidate compound for the treatment of tumor necrosis factor (TNF)-dependent chronic inflammatory conditions.


OBJECTIVE
The aim of this study was to evaluate the effects of RC-3095 in a rat model of ulcerative colitis.


METHODS
Ninety Wistar rats were included in the study. Colitis was induced by a single intracolonic application of acetic acid. Rats were divided into three groups of treatment: subcutaneous RC-3095, intracolonic mesalazine, and subcutaneous dexamethasone. Additionally, there was a fourth group of animals submitted to induction of colitis without receiving any form of treatment, and a fifth group in which no colitis was induced. Seventy-two hours after instillation of acetic acid, the animals were killed and the following parameters were assessed: morphological score of damage, histological score of colonic inflammation, and immunohistochemical expression of TNF-alpha and interleukin (IL)-1beta.


RESULTS
RC-3095 was the only treatment to significantly reduce macroscopic and microscopic scores of inflammation as compared with the animals from the non-treated colitis group. RC-3095 also significantly reduced the colonic expression of TNF-alpha, but not the expression of IL-1beta.


CONCLUSIONS
RC-3095 reduced the colitis severity in a well-established experimental model of IBD. The anti-inflammatory activity of this compound was associated with a reduction in the colonic expression of TNF-alpha. These results suggest that interference with GRP pathway might represent a potential new strategy for the treatment of ulcerative colitis that deserves further investigational studies.
Damin
Daniel C
DC
Division of Coloproctology, Hospital de Clinicas de Porto Alegre, Department of Surgery, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. damin@terra.com.br
Santos
Frederico S
FS
Heck
Renata
R
Rosito
Mário A
MA
Meurer
Luise
L
Kliemann
Lúcia M
LM
Roesler
Rafael
R
Schwartsmann
Gilberto
G
D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000473:pathology; D005260:Female; D019886:Gastrin-Releasing Peptide / Q000037:antagonists & inhibitors; D007150:Immunohistochemistry; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D010446:Peptide Fragments; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D019886:Gastrin-Releasing Peptide; D001839:Bombesin