PROGESTERONE TREATMENT POSITIVE EFFECTS IN THE FUNCTION AND INFLAMMATION OF INTESTINE COMPROMISED BY AORTIC OCCLUSION

ABSTRACT: Aortic surgery induces severe ischemia and reperfusion. Ischemia/reperfusion (I/R) is a critical medical issue due to its high sensitivity tissue damage, inflammation, mucosal injury, and motility impairment. Studies have demonstrated that female sex hormones modulate the inflammatory response triggered by I/R. Progesterone (P4) had positive effects on intestines after trauma. We evaluated the effects of P4 on intestinal function and inflammation in a model of I/R by aortic occlusion. Methods Male Wistar rats were randomized to the following four groups: sham, surgically manipulated; IR, animals subjected to I/R; P4 pre, animals treated with P4 30 min before I/R and P4 post, treated immediately after flow reestablishment. I/R was induced by catheter 2F insufflation in the descending aorta, occluded for 30 min, followed by reperfusion for 2 h. Intestinal function, inflammatory and apoptosis markers, and mesenteric microcirculation were analyzed. Results Aortic occlusion led to systemic changes and intestinal homeostasis disruption. The I/R decreased the gastrointestinal transit (sham 69%, IR 46%, P = 0.0014) and the progesterone reduced impact induced by I/R (IR 46%, P4 post 60%, P = 0.0461). The treatment prevented the increase of epithelial mucosal barrier permeability and edema formation triggered by I/R (sham 0.2770 ng/mL vs. I/R 5.455 ng/mL, P = 0.0048) and (P4 pre 2.027 ng/mL, P = 0.0393). It also reduced inflammatory cell infiltration to intestinal tissue (IR 0.5876 vs. P4 pre 0.1818, P = 0.0003 and P4 post 0.1393 stained area/tissue area, P < 0.0001), modulating the release of inflammatory mediators and apoptosis markers (IR 0.1806 vs. P4 pre 0.0468, P = 0.0452). Conclusion Progesterone treatment was effective in modulating the neutrophil response and other inflammatory markers, decreased apoptosis, and improved gastrointestinal function triggered by I/R.