Evaluation of pro-resolution pathways in DSS-induced experimental Colitis

• Grant number: 22/09393-4
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2023
• End date: January 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Raquel Franco Leal
• Grantee: Raquel Franco Leal
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Licio Augusto Velloso ; Maria de Lourdes Setsuko Ayrizono

Abstract

Inflammatory Bowel Diseases (IBD) are idiopathic chronic inflammation of the gastrointestinal tract. In recent decades, they have gained relevance due to a significant increase in their incidence and prevalence. Currently, the IBD treatment is based on drugs that act on anti-inflammatory pathways, with several cases with non-responsive patients or with significant side effects. Given this fact, new therapeutic approaches have been studied, highlighting those seeking to act on endogenous inflammation resolution mechanisms. The resolution of inflammation is an active process, driven by the synthesis of pro-resolving lipid mediators. Possible changes in the pathway of these mediators can perpetuate the inflammatory process and cause changes in the intestinal mucosa. Thus, this study aims to use the animal model of intestinal inflammation to evaluate the changes found in the inflammatory and resolutive profile during inflammation of the intestinal mucosa and to investigate the therapeutic effect of the pro-resolving lipid mediator, Resolvin D2 (RvD2). For that, C57/BL6 male mice will be used, divided into a control group and an experimental group, which will receive only drinking water and drinking water with Dextran Sodium Sulfate (DSS), for 7 days. Subsequently, experimental colitis will be induced in four groups, which will be treated intraperitoneally with RvD2 0.3¼g/animal/4 days, RvD2 1¼g/animal/4 days, anti-TNF± 5mg/Kg/single dose or saline solution. Throughout the protocols, weight, intake, and the Disease Activity Index (DIA) will be evaluated. Afterward, samples from the intestinal mucosa will be collected for the characterization of the biosynthesis pathway and RvD2 activity, through real-time PCR, immunohistochemistry, and lipidomic analysis. The inflammatory profile of these mice with DSS-induced colitis and treated with resolvin D2 will also be evaluated. The study was approved by the Unicamp Ethics Committee on the Use of Animals (CEUA, 4919-1/2018). (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CHAIM, FABIO HENRIQUE MENDONCA; PASCOAL, LIVIA BITENCOURT; DE CASTRO, MARINA MOREIRA; PALMA, BRUNA BIAZON; RODRIGUES, BRUNO LIMA; FAGUNDES, JOAO JOSE; MILANSKI, MARCIANE; LOPES, LUIZ ROBERTO; LEAL, RAQUEL FRANCO. The resolvin D2 and omega-3 polyunsaturated fatty acid as a new possible therapeutic approach for inflammatory bowel diseases. SCIENTIFIC REPORTS, v. 14, n. 1, p. 13-pg., 2024-11-20. (22/09393-4, 19/07095-3)