ABSTRACT
BACKGROUND/AIMS: Intestinal 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. METHODS: The 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. RESULTS: The 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. CONCLUSIONS: E2 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.
Subject(s)
Animals , Humans , Male , Mice , Azoxymethane , Blotting, Western , Claudin-4 , Colitis , Colitis, Ulcerative , Colon , Colonic Neoplasms , Cytokines , Enzyme-Linked Immunosorbent Assay , Eosine Yellowish-(YS) , Epithelial Cells , Estradiol , Estrogens , Hematoxylin , Inflammation , Inflammatory Bowel Diseases , Mucin-2 , Mucin-4 , Occludin , Permeability , Peroxidase , Real-Time Polymerase Chain Reaction , RNA, Messenger , Sodium , Tight JunctionsABSTRACT
BACKGROUND/AIMS: The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. METHODS: The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. RESULTS: All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. CONCLUSIONS: SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.
Subject(s)
Animals , Male , Rats , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Arachidonate 5-Lipoxygenase/drug effects , Calcitonin Gene-Related Peptide/drug effects , Cyclooxygenase 1/drug effects , Cyclooxygenase 2/drug effects , Disease Models, Animal , Gastric Mucosa/chemistry , Group IV Phospholipases A2/drug effects , Momordica/chemistry , Peroxidase/drug effects , Plant Extracts/pharmacology , Rats, Sprague-Dawley , Seeds/chemistry , Stomach Ulcer/chemically induced , Treatment OutcomeABSTRACT
BACKGROUND/AIMS: This study was performed to evaluate whether the prevalence rates of primary antibiotic resistance in Helicobacter pylori (H. pylori) isolates and the eradication rate of H. pylori could be different between cancer and non-cancer patients. METHODS: H. pylori were isolated from gastric mucosal biopsy specimens obtained from 269 Koreans, who did not have any eradication therapy history and were diagnosed as one of the following diseases; chronic gastritis, benign gastric ulcer, duodenal ulcer or gastric cancer. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin were examined with the agar dilution method. In addition, eradication rate of H. pylori was evaluated. RESULTS: There was no significant difference in the primary antibiotic resistance to above eight antibiotics among chronic gastritis, peptic ulcer disease and gastric cancer. Furthermore there was no difference of antibiotic resistance between cancer and non-cancer patients, and there was no difference of eradication rate of H. pylori according to disease. CONCLUSIONS: Primary antibiotic resistance and H. pylori eradication rate were not different between cancer and non-cancer patients.