| Title | Effects of the Gastrin-Releasing Peptide Antagonist RC-3095 in a Rat Model of Ulcerative Colitis. | | Author(s) | Damin DC, Santos FS, Heck R, Rosito MA, Meurer L, Kliemann LM, Roesler R, Schwartsmann G | | Institution | Division of Coloproctology, Hospital de Clinicas de Porto Alegre, and Department of Surgery, Room 600, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre, RS, 90 035-903, Brazil, damin@terra.com.br. | | Source | Dig Dis Sci 2009 Nov 6. | | Abstract | 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.
AIM: 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19894117 |
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