Intestinal microbiota and barrier function influence on dexamethasone-induced arterial stiffness in rats

• Grant number: 20/03380-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2021
• End date: August 31, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Sandra Lia do Amaral Cardoso
• Grantee: Alison Pires de Oliveira Lara
• Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil

Abstract

It has been shown that intestinal microbiota has a great relationship with the immunity of an individual, achieving relevance in many cardiovascular diseases. The intestinal barrier function is essential to the control of pathogens entry into the vascular system. One of these pathogens is the lipopolysaccharide, a pro-inflammatory endotoxin. In the literature, a systemic inflammation state is already well correlated with an increase in arterial stiffness, an important indicator of cardiovascular health. On the other hand, chronic treatment with dexamethasone (DEX), a synthetic glucocorticoid, can increase arterial stiffness. Since there is an apparent relationship between these variables, the aim of this study is to analyze the intestinal microbiota and barrier function influence on dexamethasone-induced arterial stiffness. The protocol will last 74 days, wherein all of these will be used for probiotic (Prob) treatment with Lactobacillus casei Shirota at 108-109 CFU, present in fermented milk Yakult®, or water by gavage and the last 14 days of protocol for subcutaneous DEX treatment at 50 ¼g/kg or saline. It will be used four groups of ten rats each: I) Control - It will receive water by gavage and subcutaneous saline; II) DEX - It will receive water by gavage and be treated with subcutaneous DEX; III) Prob - It will be treated with Prob and receive subcutaneous saline and IV) DEXProb - It will be treated with both DEX and Prob, being that, during the last 14 days, the treatments will be concomitant. As barrier function analysis, protein level of tight junction proteins - ZO-1, claudin-1 and occludin will be analyzed by Western Blotting procedures in the distal colon. Pulse Wave Velocity (PWV) and aorta collagen (COL) I, COL III and elastin protein levels will be measured. Results will be presented as means ± mean standard error (MSE). Two way analysis of variance (ANOVA) will be utilized and, for results with interaction, a Tukey post hoc will be used (p<0.05).