title: 17β-Estradiol prevents mesenteric injury induced by occlusion of the proximal descending aorta in male rats.
abstract: In surgical aortic repair or cardiac surgery with aorta occlusion, the occurrence of mesenteric ischemia and bowel injury has been associated with higher short-term mortality. The vascular protection of estrogens has been investigated and is mainly mediated by increasing the availability of nitric oxide (NO). Therefore, this study investigated the role of 17β-estradiol on visceral ischemia-reperfusion (I/R) injury after descending aorta occlusion in male rats.
  
  
  
  Mesenteric ischemia was induced in male Wistar rats by placing a 2F Fogarty arterial embolectomy catheter (Edwards Lifesciences, Irvine, Calif) in the descending aorta, which remained occluded for 15 minutes, followed by reperfusion for up to 2 hours. Rats were divided into four groups: (1) rats that underwent surgical manipulation only (sham, n = 22); (2) rats that underwent I/R injury (n = 22); (3) rats treated with intravenous 17β-estradiol (280 μg/kg) 30 minutes before I/R (n = 22); (4) or at the beginning of reperfusion (n = 22). Intestinal histopathologic changes were evaluated by histomorphometry. Mesenteric microcirculatory alterations were assessed by laser Doppler flowmetry and intravital microscopy technique. Protein expression of intercellular adhesion molecule-1, P-selectin, endothelial NO synthase (eNOS), and endothelin-1 was evaluated by immunohistochemistry; in addition, eNOS and endothelin-1 gene expressions were quantified by real-time polymerase chain reaction. Serum cytokines were measured by enzyme-linked immunosorbent assay.
  
  
  
  Relative to the sham group, the I/R group exhibited a highly pronounced loss of intestine mucosal thickness, a reduction in mesenteric blood flow (P = .0203), increased migrated leukocytes (P < .05), and high mortality rate (35%). Treatment with 17β-estradiol before aorta occlusion preserved intestine mucosal thickness (P = .0437) and mesenteric blood flow (P = .0251), reduced the number of migrated leukocytes (P < .05), and prevented any fatal occurrence. Furthermore, 17β-estradiol downregulated the expression of intercellular adhesion molecule-1 (P = .0001) and P-selectin (P < .0001) on the endothelium and increased the protein expression of eNOS (P < .0001). The gene expressions of eNOS and endothelin-1 did not differ between the groups.
  
  
  
  The prophylactic treatment with 17β-estradiol showed better overall repercussions and was able to prevent any fatal occurrence, increase eNOS expression, thus preserving mesenteric perfusion and intestinal integrity, and reduce inflammation.
authors.affiliation: Heart Institute (InCor), LIM 11, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Paulo Thales
authors.initials: PT
authors.lastname: Rocha de Sousa
authors.affiliation: Heart Institute (InCor), LIM 11, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Breithaupt-Faloppa
authors.affiliation: Heart Institute (InCor), LIM 11, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Cristiano
authors.initials: C
authors.lastname: de Jesus Correia
authors.affiliation: Heart Institute (InCor), LIM 11, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Raif Restivo
authors.initials: RR
authors.lastname: Simão
authors.affiliation: Heart Institute (InCor), LIM 11, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Sueli Gomes
authors.initials: SG
authors.lastname: Ferreira
authors.affiliation: Heart Institute (InCor), LIM 11, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Alfredo Inácio
authors.initials: AI
authors.lastname: Fiorelli
authors.affiliation: Heart Institute (InCor), LIM 11, University of São Paulo Medical School, São Paulo, São Paulo, Brazil.
authors.forename: Luiz Felipe Pinho
authors.initials: LFP
authors.lastname: Moreira
authors.affiliation: Heart Institute (InCor), LIM 11, University of São Paulo Medical School, São Paulo, São Paulo, Brazil. Electronic address: exppaulina@incor.usp.br.
authors.forename: Paulina
authors.initials: P
authors.lastname: Sannomiya
mesh_terms: D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D021721:Balloon Occlusion / Q000009:adverse effects*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D007082:Ileum / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D065666:Mesenteric Ischemia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects*; D013997:Time Factors
chemical_list: D019332:Endothelin-1; C000609942:ICAM1 protein, rat; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D004958:Estradiol; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat