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Study of the modulatory action of crotoxin on the evolution of experimental ulcerative Colitis

Grant number: 22/02512-8
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2022
Effective date (End): December 31, 2022
Field of knowledge:Biological Sciences - Immunology - Immunogenetics
Principal Investigator:Orlando Garcia Ribeiro Filho
Grantee:Raquel Guedes de Oliveira Brito
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Ulcerative colitis (UC) is an inflammatory disease characterized by a chronic process of colonic mucosa damage. It is associated with an increased risk of carcinogenesis. The pathogenesis of the disease involves environmental and genetic factors with the active participation of phagocytic inflammatory cells, mainly activated macrophages. The most appropriate experimental study model for ulcerative colitis has been performed by ingesting sodium dextran sulfate (DSS) in susceptible animals. Mice phenotypically selected for high (AIRmax) or low (AIRmin) acute inflammatory response to subcutaneous Biogel exhibit different behaviors to DSS ingestion, with AIRmax animals being more susceptible to the development of DSS-induced UC. The exact mechanism by which DSS induces UC is not well understood. However, there is a demonstration that DSS alters the intestinal epithelial barrier leading to an inflammatory reaction and causing disruption of intestinal crypts and aggression to epithelial cells, thus increasing the permeability of the epithelial barrier. This process allows the encounter of the intestinal microbiota with the granulocytes present in the underlying mucosa, causing inflammation and ulceration and, subsequently, tissue healing and repair. Thus, we will study the direct action of DSS on the colon mucosa in animals selected for RIA, in the presence or not of Crotoxin, a factor from Crotalus durisus terrificus venom, analyzing the distal segments of the colon concerning cellular dynamics. The study will evaluate clinical parameters involved in UC, known as IAD (disease activity index), and immunological aspects, specifically cellular dynamics, aiming at identifying therapeutic targets for the control of this pathology.(AU)

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