Effects of 17beta;-Estradiol on Colonic Permeability and Inflammation in an Azoxymethane/Dextran Sulfate Sodium-Induced Colitis Mouse Model

Abstract

Background/AimsIntestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model.MethodsThe effects of 17β-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions.ResultsThe colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p<0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-κB, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2.ConclusionsE2 acts through the estrogen receptor β signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines.

A Modified Formulation of Sutaehwan Ameliorates Menopausal Anxiety, Depression and Heart Hypertrophy in the VCD-Induced Menopausal Mouse Model

“…26) Conversely, although estradiol improved the behavior of anxiety and depression in postmenopausal animal models, but it did not increase the expression of BDNF in the brain. 27) In addition, they compared the administration methods via subcutaneous (SC) and intracerebroventricular (ICV) route to examine therapeutic effect of estrogen on anxiety and depressive phenotypes in the postmenopausal mice model. In the study, ICV administration of estradiol shows a significant increase in the number of crosses into the central area but not SC, implying that depending on the concentration of estrogen that reaches the brain, the results of behavioral testing may vary.…”

A comparative study on pharmacokinetics and tissue distribution of 5-hydroxy-4-methoxycanthin-6-one and its metabolite in normal and dextran sodium sulfate-induced colitis rats by HPLC-MS/MS

“…[ 29 ] The absorption of drugs was affected by the pathological changes in gastrointestinal tract, the main place for drug absorption. In the case of intestinal mucosal damage, the expression of tight junction proteins between cells was reduced, and intestinal permeability was increased, [ 30 ] which could facilitate the penetration of material. The increasing evidence suggested that a dysregulation of the protease/antiprotease balance in the gut contributed to epithelial damage and increases permeability.…”

Expression of Neurotrophic Factors, Tight Junction Proteins, and Cytokines According to the Irritable Bowel Syndrome Subtype and Sex

“…An automatic immunostainer (BenchMark XT; Ventana Medical Systems, Inc, Tucson, AZ, USA) and an UltraView Universal DAB detection kit (Ventana Medical Systems) were used for immunostaining. 22 Expression percentage was assessed as a ratio between the number of cells stained with ZO-1 divided by the total number of cells counted in a section. ZO-1 expression was quantified using ImageJ 1.50i software.…”