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Role of histamine receptor H1 in intestinal epithelial barrier dysfunction induced by sepsis

Grant number: 22/14864-6
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2023
Effective date (End): April 30, 2024
Field of knowledge:Biological Sciences - Morphology - Histology
Principal Investigator:Rafael Simone Saia
Grantee:Mauê Ananda de Lima Sanas
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Sepsis is a multifactorial syndrome caused by an unbalanced host response to infection. The intestinal epithelial barrier allows selective permeation of molecules and ions and prevents the passage of microorganisms from the lumen into the blood and lymph stream. However, the inflammatory response can induce increased intestinal permeability, which leads to potential systemic dissemination of microorganisms and their antigens and multiple organ dysfunction. Mast cells and the mediators they release, such as histamine, play an important role in intestinal homeostasis and participate in the activation and regulation of inflammatory responses in sepsis. Thus, this study aims to elucidate the role of histamine, via H1 receptor, in lesions of the intestinal epithelial barrier in sepsis in mice. For this, the animals will be treated with desloratadine and then sepsis will be induced with the PLC model, and samples will be collected for the quantification of inflammatory mediators and the determination of intestinal permeability. Our hypothesis is that treatment with the H1 receptor antagonist will negatively modulate the inflammatory response, intestinal permeability and bacterial translocation.

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