Estradiol prevented intestinal ischemia and reperfusion-induced changes in intestinal permeability and motility in male rats.

OBJECTIVES: Ischemia and reperfusion (I/R) in the intestine could lead to severe endothelial injury, compromising intestinal motility. Reportedly, estradiol can control local and systemic inflammation induced by I/R injury. Thus, we investigated the effects of estradiol treatment on local repercussions in an intestinal I/R model. METHODS: Rats were subjected to ischemia via the occlusion of the superior mesenteric artery (45 min) followed by reperfusion (2h). Thirty minutes after ischemia induction (E30), 17ß-estradiol (E2) was administered as a single dose (280 µg/kg, intravenous). Sham-operated animals were used as controls. RESULTS: I/R injury decreased intestinal motility and increased intestinal permeability, accompanied by reduced mesenteric endothelial nitric oxide synthase (eNOS) and endothelin (ET) protein expression. Additionally, the levels of serum injury markers and inflammatory mediators were elevated. Estradiol treatment improved intestinal motility, reduced intestinal permeability, and increased eNOS and ET expression. Levels of injury markers and inflammatory mediators were also reduced following estradiol treatment. CONCLUSION: Collectively, our findings indicate that estradiol treatment can modulate the deleterious intestinal effects of I/R injury. Thus, estradiol mediates the improvement in gut barrier functions and prevents intestinal dysfunction, which may reduce the systemic inflammatory response.

Estradiol prevented intestinal ischemia and reperfusion-induced changes in intestinal permeability and motility in male rats

OBJECTIVES: Ischemia and reperfusion (I/R) in the intestine could lead to severe endothelial injury, compromising intestinal motility. Reportedly, estradiol can control local and systemic inflammation induced by I/R injury. Thus, we investigated the effects of estradiol treatment on local repercussions in an intestinal I/R model. METHODS: Rats were subjected to ischemia via the occlusion of the superior mesenteric artery (45 min) followed by reperfusion (2h). Thirty minutes after ischemia induction (E30), 17β-estradiol (E2) was administered as a single dose (280 μg/kg, intravenous). Sham-operated animals were used as controls. RESULTS: I/R injury decreased intestinal motility and increased intestinal permeability, accompanied by reduced mesenteric endothelial nitric oxide synthase (eNOS) and endothelin (ET) protein expression. Additionally, the levels of serum injury markers and inflammatory mediators were elevated. Estradiol treatment improved intestinal motility, reduced intestinal permeability, and increased eNOS and ET expression. Levels of injury markers and inflammatory mediators were also reduced following estradiol treatment. CONCLUSION: Collectively, our findings indicate that estradiol treatment can modulate the deleterious intestinal effects of I/R injury. Thus, estradiol mediates the improvement in gut barrier functions and prevents intestinal dysfunction, which may reduce the systemic inflammatory response.

Acute lung injury induced by intestinal ischemia and reperfusion is altered in obese female mice.

RATIONAL: Acute lung injury (ALI) is a common complication after intestinal ischemia and reperfusion (I/R) injury that can lead to acute respiratory distress syndrome (ARDS). We have previously demonstrated that females are protected against lung damage induced by intestinal I/R through an estrogen mediated mechanism. OBJECTIVES: To investigate the effect of obesity on ALI induced by intestinal I/R in female mice. METHODS: C57Bl/6 female mice were fed with a standard low-fat diet (SD) or a high-fat diet (HFD) for 9 weeks. Intestinal I/R injury was induced by a 45 min occlusion of the mesenteric artery followed by 2 and 24 h of reperfusion. RESULTS: Significant increase in lung myeloperoxidase expression (MPO) and neutrophil numbers of SD and HFD mice occurred at 2 h and 24 h of reperfusion. Furthermore, HFD mice presented a significant increase in lung eosinophil peroxidase (EPO) expression and eosinophil numbers compared to SD mice. Lung wet/dry weight ratio was significantly greater in HFD mice at 2 and 24 h of reperfusion, accompanied by a significant increase in the expression of inducible NO in the lung tissue and a significant decrease in arterial oxygen saturation at 24 h of reperfusion relative to SD mice. CONCLUSION: Obesity predisposes female mice to increased pulmonary oedema and deterioration in gas exchange, which is accompanied by an increase in iNOS expression in the lung.

Estradiol mediates the long-lasting lung inflammation induced by intestinal ischemia and reperfusion.

BACKGROUND: Lung inflammation is one of the main consequences of intestinal ischemia reperfusion (intestinal IR) and, in severe cases, can lead to acute respiratory distress syndrome and death. We have previously demonstrated that estradiol exerts a protective effect on lung edema and cytokine release caused by intestinal IR in male rats. MATERIALS AND METHODS: We investigated the role of estradiol on the generation of interleukin (IL)-1ß, IL-10, vascular endothelial growth factor (VEGF), and cytokine-induced neutrophil chemoattractant 1 (CINC-1) in a female rat model of intestinal IR. Blood and bone marrow leukocytes were also quantified. Seven-days-ovariectomized rats were subjected to intestinal IR by occlusion of the superior mesenteric artery for 45 min. After reperfusion of the tissue for 2 h, the rats were sacrificed. Lung tissue was collected, cultured for 24 h and assayed. RESULTS: We observed a significant increase in serum levels of IL-10, CINC-1, uric acid and circulating, but not bone marrow, leukocyte numbers. In addition, intestinal IR induced a significant increase in the ex-vivo lung levels of IL-1ß, IL-10, and VEGF. Treatment with 17ß-estradiol before the induction of intestinal IR prevented the systemic release of IL-10, CINC-1, and uric acid, but it did not affect the leukocytosis. In addition, 17ß-estradiol significantly prevented the ex-vivo release of IL-1ß and VEGF from lung tissue. CONCLUSIONS: We demonstrated that intestinal IR interferes with lung homeostasis, priming the tissue to generate proinflammatory mediators for at least 24 h postischemia. Furthermore, our data confirm that the inflammatory responses caused by intestinal IR are estradiol mediated.

Estradiol Modulates Local Gut Injury Induced by Intestinal Ischemia-Reperfusion in Male Rats.

Intestinal ischemia and reperfusion (I/R) triggers a systemic inflammatory response characterized by leukocyte mobilization from the bone marrow, release of cytokines to the circulation, and increased microvascular permeability, leading to high mortality. Females have shown attenuated inflammatory response to trauma when compared with males, indicating a role for female sex hormones in this process. Here, we have evaluated the effect of estradiol on the local gut injury induced by I/R in male rats. I/R was induced by the clamping of the superior mesenteric artery for 45 min, followed by 2 h of reperfusion. A group received 17ß-estradiol (280 µg/kg, i.v., single dose) at 30 min of ischemia. Morphometric analysis of the gut showed I/R induced a reduction of villous height that was prevented by estradiol. White blood cells, notably granulocytes, were mobilized from the circulation to the intestine by I/R, which was also prevented by estradiol treatment. Groups had the intestine wrapped in a plastic bag to collect intestinal fluid, where leukocytes count, TNF-α, and IL-10 levels were increased by I/R. Serum chemokines (CINC-1, MIP-1α, MIP-2), ICAM-1 expression in the mesenteric tissue, and neutrophils spontaneous migration measured in vitro were also increased after I/R. Estradiol treatment reduced leukocytes numbers and TNF-α on intestinal fluid, serum chemokine release and also downregulated MIP-1α, MIP-2 gene expression, and spontaneous in vitro neutrophil migration. In conclusion, estradiol blunts intestinal injury induced by I/R by modulating chemokines release and leukocyte trafficking.