Anthocyanidins: investigation of mechanisms involved in intestinal permeability

• Grant number: 21/11109-0
• Support Opportunities: Scholarships abroad - Research
• Start date: March 28, 2022
• End date: March 27, 2023
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Raquel de Cássia dos Santos
• Grantee: Raquel de Cássia dos Santos
• Host Investigator: Wallace MacNaughton
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil
• Institution abroad: University of Calgary, Canada

Abstract

Peptic ulcers are lesions that affect both the gastric and duodenal tissue and the number of cases grows as a result of the use of non-steroidal anti-inflammatory drugs (NSAIDs) used to treat various chronic diseases, in addition to inappropriate habits, such as excessive alcohol consumption and smoking. Since the discovery and implementation of the use of proton pump inhibitors (PPI), the incidence of gastric ulcers has reduced, however, there has been an increase in intestinal lesions since PPIs do not guarantee protection to the intestine. The epithelium is damaged during intestinal inflammation due to the action of inflammatory cytokines such as TNF resulting in ulceration. To protect the deeper layers of the intestinal wall, the intestinal barrier tightly regulates the passage of pro-inflammatory molecules, microorganisms, toxins, and antigens. Malvidin and cyanidin have been shown to be effective against duodenal ulcers induced by a triad called polypharmacy (combination of PPI and NSAID) and intestinal ulcers induced by acetic acid (Fapesp 2016-20600-0), reducing the presence of inflammatory mediators in the intestine. However, the mechanism of action in which this repair takes place is not clear. Thus, the aim of this work is to investigate the action of malvidin and cyanidin on the intestinal mucosa regarding the ability to maintain its integrity and whether these actions justify the results observed so far. Therefore, cell tests will be carried out to analyze whether the observed intestinal protection is related to the maintenance of intestinal integrity through tests of the models of cell viability, apoptosis, wound healing, EdU Proliferation assay, permeability tests using the Ussing chambers (calcium switch and cytokine treatment) and organoids. The results obtained will provide relevant information about the mechanisms of action involved in the pharmacological activity of these molecules and will contribute to the future development of these compounds as a therapeutic option in the treatment of gastrointestinal diseases. (AU)