Effect of treatment with codrugs acting on H4 receptors associated with mesalazine on DSS-induced colitis in mice

• Grant number: 24/15451-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Richardt Gama Landgraf
• Grantee: Pamella Soares Silva
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

Crohn's disease and ulcerative colitis are the most common forms of inflammatory human intestinal disease, being chronic pathologies that affect individuals throughout life. The genetic factor is identified as the main responsible for intestinal inflammation, linked to environmental conditions, immune system dysregulation and interaction with the intestinal microbiota. The most common manifestations of intestinal inflammation are: abdominal pain, bloody diarrhoea, weight loss, loss of appetite, anorexia and fever. When the disease develops in childhood, growth and development retardation can occur. In addition, the exact causes of colitis are still not completely known, but from molecular assessments, during the disease progression, changes in the immune system, intestinal microbiota, rupture of the mucosal barrier, increased levels of inflammatory cytokines and oxidative stress are observed. The fundamental role of the H4 receptor in the respiratory tract and intestinal diseases has been demonstrated. These receptors may be associated with the regulation of several defense cells such as mast cells, basophils, eosinophils, lymphocytes, macrophages, and epithelial cells during the development of the inflammatory process. Existing data are still incomplete but indicate a pro-inflammatory participation of H4Rs in colitis models, suggesting a new and important therapeutic target in the treatment of this disease. Thus, the aim of this project is to evaluate the anti-inflammatory activity of H4 receptor antagonist compounds developed by our group, which has already demonstrated anti-inflammatory potential in a model of inflammatory bowel disease, and to associate it with anti-inflammatory agents already used in the therapy of inflammatory bowel diseases (such as mesalazine), leading to a synergistic action of an H4 antagonist and a classic anti-inflammatory.