Effect of treatment with H3/H4 receptor antagonist in colitis induced by DSS in mice

• Grant number: 20/16258-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2021
• Effective date (End): April 30, 2022
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Richardt Gama Landgraf
• Grantee: Beatriz Klahold Lippi
• 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 H3 / H4 receptor antagonist compounds developed by our group that has already demonstrated anti-inflammatory potential in a model of pulmonary inflammatory disease. (AU)