Renata Heck
Universidade Federal do Rio Grande do Sul
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Digestive Diseases and Sciences | 2010
Daniel de Carvalho Damin; Frederico Sedrez dos Santos; Renata Heck; Mario Antonello Rosito; Luíse Meurer; Lucia Maria Kliemann; Rafael Roesler; Gilberto Schwartsmann
BackgroundRC-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.AimThe aim of this study was to evaluate the effects of RC-3095 in a rat model of ulcerative colitis.MethodsNinety 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-α and interleukin (IL)-1β.ResultsRC-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-α, but not the expression of IL-1β.ConclusionsRC-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-α. 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.
Journal of Clinical Gastroenterology | 2009
Daniel de Carvalho Damin; Frederico Sedrez dos Santos; Renata Heck; Gilberto Schwartsmann
To the Editor: We read with great interest the article by Katz, in which the author reviewed in a very objective and comprehensive manner the results from the main placebo-controlled trials evaluating currently available treatment approaches for the management of patients with inflammatory bowel disorders (IBD). By identifying the so-called gaps (ie, the percentage of patients lacking any benefit) of the current available treatments, the author was able to demonstrate that most drugs will be effective only in 50% of patients, with response rates of 50% to 60% and remission rates of 20% to 30%. Therefore, the identification of novel therapeutic strategies for patients with IBD is urgently needed. In that sense, we would like to propose that the inhibition of the gastrinreleasing peptide (GRP) receptordependent signaling pathway might represent a potentially valuable approach to be exploited in these conditions. The GRP belongs to the bombesinlike peptide family, mainly found in neurons of the human stomach and intestine. These peptides are responsible for a variety of central and peripheral functions. In the gastrointestinal tract, they promote secretion of hormones (gastrin, somatostatin) and pancreatic enzymes, and stimulate smooth muscle contraction. Preclinical studies have shown that GRP possesses immune-regulatory functions, such as chemoattraction of macrophages and lymphocytes, and stimulation of cell-mediated cytotoxicity and natural killer activity. Recently, our group has reported that RC-3095, a synthetic GRP receptor antagonist, was able to attenuate the release of proinflammatory cytokines (tumor necrosis factor-a and interleukin-1b) in vitro and in vivo, improving survival of rats in a well-established model of sepsis. Our findings strongly suggest the involvement of a GRP receptor-dependent signaling pathway in the activation of the inflammatory cascade in sepsis. On the basis of these observations, we started a series of experiments to evaluate the therapeutic potential of RC-3095 in tumor necrosis factordependent and interleukin-1–dependent preclinical models for chronic inflammatory disorders, such as rheumatoid arthritis and ulcerative colitis, with very provocative results. In a rat model for inflammatory colitis, induced by intracolonic administration of 5% acetic acid, daily subcutaneous administration of RC-3095 produced a marked improvement in the inflammatory changes. The lesions were blindly scored according to macroscopic analyses and quantified as ulcer index (Figs. 1, 2). Although histologic and molecular analyses are still pending, the beneficial effect observed in the macroscopic evaluation of the removed colon among animals treated with RC3095, as compared with animals receiving only intracolonic saline solution, suggests that GRP receptor may be exploited as a potential therapeutic target in future studies evaluating new treatment options for IBD. Further investigations are warranted.
Archive | 2011
Luiz Edmundo Mazzoleni; Guilherme Becker Sander; Felipe Mazzoleni; Laura Renata de Bona; Tobias Cancian Milbradt; Otávio Berwanger; Mathias Bressel; Maria Isabel Albano Edelweiss; Stela Scaglioni Marini; Cynthia Goulart Molina; Luciano Folador; Roberta Perin Lunkes; Renata Heck; Oscar Augusto Birkhan; Bianca Michel Spindler; Natan Katz; Bruno da Silveira Colombo; Luiza Brusius Renck; Elisa Grando; Bianca Hocevar de Moura; Franciele Darsie Dahmer; Juliano Rauber
Journal of Clinical Gastroenterology | 2009
Daniel de Carvalho Damin; Frederico Sedrez dos Santos; Renata Heck; Gilberto Schwartsmann
Archive | 2007
Felipe Mazzoleni; Luiz Edmundo Mazzoleni; Diego de Mendonça Uchôa; Maria Isabel Albano Edelweiss; Luíse Meurer; Guilherme Becker Sander; Bianca Hocevar; Bianca Michel Spindler; Bruno da S. Colombo; Elisa Grando; Fabiana Costa Menezes; Franciele Darsie Dahmer; Israel de Quadros Cardoso; Luciano Folador; Luiza Brusius Renck; Renata Heck; Roberta P. Lunker; Cristiano Andre da Silva; Candice Franke Krumel; Rachel Zenker; Laura Renata de Bona
Archive | 2007
Felipe Mazzoleni; Renata Heck; Guilherme Becker Sander; Carlos Fernando de Magalhães Francisconi; Alexandro L. Theil; Luíse Meurer; Diego de Mendonça Uchôa; Maria Isabel Albano Edelweiss; Luiza Brusius Renck; Elisa Grando; Camila J. Lopes; Bruno da S. Colombo; Franciele Darsie Dahmer; Tobias Cancian Milbradt; Luiz Edmundo Mazzoleni
Archive | 2007
Felipe Mazzoleni; Renata Heck; Guilherme Becker Sander; Carlos Fernando de Magalhães Francisconi; Alexandro L. Theil; Natan Katz; Analia Maldonado; Luiza Brusius Renck; Camila J. Lopes; Bruno da Silveira Colombo; Franciele Darsie Dahmer; Maria Luiza B Sanchotene; Raquel Petrucci Zenker; Josiane Fischer; Luiz Edmundo Mazzoleni
Archive | 2007
Renata Heck; Frederico Sedrez dos Santos; Daniel de Carvalho Damin; Mario Antonello Rosito; Rafael Roesler; Gilberto Schwartsmann
Archive | 2007
Guilherme Becker Sander; Renata Heck; Carlos Fernando de Magalhães Francisconi; Alexandro L. Theil; Felipe Mazzoleni; Luciano Folador; Cynthia Goulart Molina; Natan Katz; Analia Maldonado; Luiza B. Henck; A. Gamarrati; Pâmela Schitz von Reisswitz; Maria Luiza Conceição Sanchotene; Luiz Edmundo Mazzoleni; Raquel Petrucci Zenker
Archive | 2007
Felipe Mazzoleni; Guilherme Becker Sander; Luiz Edmundo Mazzoleni; Bruno da Silveira Colombo; Cynthia Goulart Molina; Fabiana Costa Menezes; Franciele Darsie Dahmer; Israel de Quadros Cardoso; Luciano Folador; Luiza Brusius Renck; Natan Katz; Oscar Augusto Birkhan; Pedro Proença Guerrieri; Renata Heck; Rachel Zenker; Stela Scaglioni Marini; Pâmela Schitz von Reisswitz; Tobias Cancian Milbradt; Laura Renata de Bona