Non-steroidal anti-inflammatory drugs (NSAIDs) are used for the management of various conditions, such as pain, fever, inflammation, cancer, or cardiovascular diseases. These drugs may induce injury throughout the gastrointestinal tract. NSAIDs are associated with diverse upper gastrointestinal adverse effects, including dyspepsia, erosions, peptic ulcer diseases and complications such as bleeding perforation. Established risk factors for these adverse effects include age, prior ulcer, types, doses and duration of NSAIDs, concurrent other NSAIDs administration, and the concomitant uses of corticosteroids or anticoagulants. Misoprostol, proton pump inhibitors, and cyclooxygenase-2 selective inhibitors have been used to reduce the risk of NSAID-associated upper gastrointestinal events. NSAID-induced enteropathy is more common than complications of the stomach and duodenum and is usually manifested by occult blood loss or hypoalbuminemia. Furthermore, NSAIDs induce small intestinal injuries causing gut barrier damage, and bacterial translocation that have been proposed to be associated with the burden of illness in decompensated chronic heart failure. However, the risk factors for NSAID-induced enteropathy and bacterial translocation, as well as its preventive measures, are not well documented.
Anti-Inflammatory Agents, Non-Steroidal/*adverse effects/therapeutic use ; Capsule Endoscopy ; Gastrointestinal Diseases/*chemically induced/diagnosis/therapy ; Humans ; Intestinal Diseases/chemically induced/diagnosis/therapy ; Risk Factors ; Upper Gastrointestinal Tract/pathology

OBJECTIVETo examine the efficacy of muscovite on non-steroidal anti-inflammatory drug (NSAID) associated intestinal injury in rats, and its influences on the expressions of inflammatory factors, tumor necrosis factor-alpha (TNF-alpha) and nuclear factor-kappaB (NF-kappaB), for researching its possible mechanism of intestinal mucosal protection.

METHODSNSAID associated intestinal injury in rat was induced by intra-gastric infusion of diclofenac. Twenty-four male Sprague-Dawley rats were randomly and equally assigned to three groups: normal control group, model control group and Muscovite group, 8 in each group. The normal control group received physiological saline 1 mL/100 g and the other two groups received diclofenac 7.8 mg/kg respectively every day for 5 days; while to the Muscovite group, Muscovite 120 mg/kg was gastric infused once on the day before modeling, followed with 120 mg/kg per day, given an hour before diclofenac infusion in the modeling days. All rats were killed on the 6th day, their gross changes and histological injury of intestinal mucosa were observed and scored, serum level of TNF-alpha was assayed in radioimmunoassay and NF-kappaB activity was determined by immunohistochemistry.

RESULTSThe small dosage diclofenac administration can cause intestinal damage, revealing obviously erythema, erosion, multiple ulcer, intestinal stricture, even perforation, etc. Intestinal injury in the Muscovite group was obviously milder than that in the model control group, only showed changes of local congestion, edema and erosion. The scores of gross and histological intestinal features in the model control group were 4.38 +/- 1.41 and 4.00 +/- 1.85, while in the Muscovite group were 1.25 +/- 1.58 and 1.75 +/- 0.71, respectively, all higher than those in the normal control group (0.00 +/- 0.00 and 0.00 +/- 0.00, P < 0.01 and P < 0.05), respectively, but the elevation in the model control group were more significant (P < 0.05). Similar results were shown in comparisons of TNF-alpha and NF-kappaB levels between groups, the values were 6.19 +/- 2.76 and 1.38 +/- 1.19 in normal control; 22.20 +/- 5.42 and 5.75 +/- 0.46 in model control; 9.61 +/- 4.02 and 0.13 +/- 0.35 in the Muscovite group, respectively (all P < 0.01).

CONCLUSIONMuscovite could effectively reduce the NSAID associated intestinal mucosal injury by inhibiting the activity of NF-kappaB in intestinal mucosa, and down-regulating the expression of TNF-alpha in blood plasma, so muscovite is proved to have protective function for intestine.

Aluminum Silicates ; therapeutic use ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; Intestinal Diseases ; chemically induced ; prevention & control ; Intestinal Mucosa ; pathology ; Intestine, Small ; pathology ; Male ; NF-kappa B ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

BACKGROUND/AIMS: We evaluated the long-term outcome and clinical course of patients of nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injury by performing capsule endoscopy (CE). METHODS: A multicenter retrospective study was conducted using data collected from the CE nationwide database registry, which has been established since 2002. RESULTS: A total of 140 patients (87 males; mean age, 60.6+/-14.8 years) from the CE nationwide database registry (n=2,885) were diagnosed with NSAID-induced small intestinal injury and enrolled in our study. Forty-nine patients (35.0%) presented with a history of aspirin use and an additional 49 (35.0%) were taking NSAIDs without aspirin. The most prominent findings after performing CE were multiple ulcerations (n=82, 58.6%) and erosions or aphthae (n=32, 22.9%). During the follow-up period (mean, 15.9+/-19.0 months; range, 0 to 106 months), NSAID-induced small intestinal injury only recurred in six patients (4.3%). Older age and hypertension were positive predictive factors for recurrence. CONCLUSIONS: These results suggest that the recurrence of NSAID-induced small bowel injury was not frequent in the presence of conservative treatment. Therefore, the initial diagnosis using CE and the medication history are important.
Age Factors ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; Aspirin/adverse effects ; *Capsule Endoscopy ; Female ; Humans ; Intestinal Diseases/chemically induced/*pathology ; Intestine, Small/*drug effects/injuries/*pathology ; Male ; Middle Aged ; Recurrence ; Republic of Korea ; Retrospective Studies ; Time Factors ; Ulcer/chemically induced/*pathology

OBJECTIVETo develop an experimental rat model of inflammatory bowel disease (IBD) by administration of dextran sulfate sodium (DSS), and to observe changes in the tight junction protein expression and permeability of colon mucosa.

METHODSMale Sprague-Dawley (SD) rats were randomly divided into control (n=27) and IBD model groups (n=27). In the IBD model group, IBD was induced by 6-day administration of 3% DSS in water followed by 14-day administration of water only. The control group was fed with water only. Pathological changes in colon mucosae were observed on days 7, 14 and 21 after DSS administration. Colon tissue specimens were collected on day 21 for measuring myeloperoxidase (MPO) activity. The transepithelial electric resistance (TEER), transepithelial potential difference (TEPD) and short circuit current (Isc) of the specimens were measured by Ussing chamber. Real-time PCR and Western blot were used to measure the mRNA and protein expression of tight junction proteins in colon epithelia.

RESULTSIn the IBD model group, diarrhea, hemafecia and weight loss were seen. Inflammation occurred mainly in the distal colon and was characterized by crypt abscess and inflammatory cell infiltration. The IBD model group showed significantly increased MPO activity (P<0.01), significantly decreased TEER (P<0.01) and TEPD (P<0.01), and significantly increased Isc (P<0.01) compared with the control group. No claudin 2 expression of mRNA and protein was detected in the control group, and they were expressed in the IBD model group. The expression levels of claudin 3, occludin and ZO-1 in the IBD model group were significantly decreased compared with in the control group (P<0.01).

CONCLUSIONSIBD rats show colonic barrier dysfunction and changes in the expression of tight junction proteins. The changes in the expression of tight junction proteins may contribute to colonic barrier dysfunction in cases of IBD in the chronic recovery stage.

Animals ; Claudin-3 ; analysis ; Colon ; metabolism ; pathology ; Dextran Sulfate ; Disease Models, Animal ; Inflammatory Bowel Diseases ; chemically induced ; metabolism ; Intestinal Mucosa ; metabolism ; Male ; Occludin ; analysis ; Permeability ; Rats ; Rats, Sprague-Dawley ; Tight Junction Proteins ; analysis ; Zonula Occludens-1 Protein ; analysis

TNF-alpha is a major cytokine involved in inflammatory bowel disease (IBD). In this study, water extract of Grifola frondosa (GFW) was evaluated for its protective effects against colon inflammation through the modulation of TNF-alpha action. In coculture of HT-29 human colon cancer cells with U937 human monocytic cells, TNF-alpha-induced monocyte adhesion to HT-29 cells was significantly suppressed by GFW (10, 50, 100 microg/ml). The reduced adhesion by GFW correlated with the suppressed expression of MCP-1 and IL-8, the major IBD-associated chemokines. In addition, treatment with GFW significantly suppressed TNF-alpha-induced reactive oxygen species production and NF-kappaB transcriptional activity in HT-29 cells. In differentiated U937 monocytic cells, LPS-induced TNF-alpha production, which is known to be mediated through NF-kappaB activation, was significantly suppressed by GFW. In an in vivo rat model of IBD, oral administration of GFW for 5 days (1 g/kg per day) significantly inhibited the trinitrobenzene sulfonic acid (TNBS)-induced weight loss, colon ulceration, myeloperoxidase activity, and TNF-alpha expression in the colon tissue. Moreover, the effect of GFW was similar to that of intra-peritoneal injection of 5-aminosalicylic acid (5-ASA), an active metabolite of sulfasalazine, commonly used drug for the treatment of IBD. The results suggest that GFW ameliorates colon inflammation by suppressing production of TNF-alpha as well as its signaling through NF-kappaB leading to the expression of inflammatory chemokines, MCP-1 and IL-8. Taken together, the results strongly suggest GFW is a valuable medicinal food for IBD treatment, and thus may be used as an alternative medicine for IBD.
Animals ; Cell Adhesion/drug effects/immunology ; Cell Extracts/administration & dosage/*pharmacology ; Chemokine CCL2/biosynthesis/genetics ; Coculture Techniques ; Colon/drug effects/*metabolism/pathology ; Grifola ; HT29 Cells ; Humans ; Inflammatory Bowel Diseases/chemically induced/*drug therapy/pathology/physiopathology ; Interleukin-8/biosynthesis/genetics ; Intestinal Mucosa/*drug effects/metabolism/pathology ; Monocytes/*drug effects/metabolism/pathology ; NF-kappa B/genetics/metabolism ; Peroxidase/metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Stomach Ulcer ; Transcription, Genetic/drug effects ; Trinitrobenzenesulfonic Acid/administration & dosage ; Tumor Necrosis Factor-alpha/*biosynthesis/genetics ; U937 Cells ; Weight Loss