JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2014, Vol. 52 ›› Issue (8): 6-13.doi: 10.6040/j.issn.1671-7554.0.2013.764

Previous Articles     Next Articles

Evaluation of NSAIDs-induced gastropathy and therapeutic effect by confocal laser endomicroscopy

WANG Han1, SHI Sha1,2, CHEN Feixue1, LI Yueyue1, CAO Jing1, ZUO Xiuli1, LI Yanqing1   

  1. 1. Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    2. Department of Gastroenterology, Liaocheng People's Hospital, Taishan Medical University, Liaocheng 252002, Shandong, China
  • Received:2013-12-23 Revised:2014-07-02 Online:2014-08-10 Published:2014-08-10

PDF (PC)

268

Abstract: Objective To explore the morphological nature and exact mechanisms of gastric mucosal barrier dysfunction underlying NSAIDs-related gastric damage by using confocal laser endomicroscopy (CLE), and to investigate how acute mucosal injuries were influenced by geranylgeranylacetone and rabeprazole. Methods After a 4-grade score system of acute gastric mucosal injury by CLE was established, the severity of NSAIDs-induced gastropathy and effect of medication were evaluated. The expressions of occludin and ZO-1 were detected. Results The CLE score was significantly increased and expression of tight junctions was down-regulated after the administration of indomethacin. Geranylgeranylacetone and rabeprazole could intervene in the damage process and protect the integrity of the epithelial barrier. Conclusion CLE can be objective, real-time and accurate in assessing the severity of NSAIDs-induced gastropathy. Geranylgeranylacetone and rabeprazole can be used as efficient prophylactic and therapeutic medications in NSAIDs-related gastropathy for their protective effect in maintaining the integrity of gastric mucosal barrier.

Key words: Confocal laser endomicroscopy, NSAIDs-induced gastropathy, Mucosal barrier dysfunction, Geranylgeranylacetone, Rabeprazole

CLC Number: 

  • R573.3
[1] Brooks P, Emery P, Evans J F, et al. Interpreting the clinical significance of the differential inhibition of COX-1 and COX-2[J]. Rheumatology, 1999, 38(8): 779-788.
[2] Bedson J, Whitehurst T, Lewis M, et al. Factors affecting over-the-counter use of aspirin in the secondary prophylaxis of cardiovascular disease[J]. Br J Gen Pract, 2001, 51(473): 1001-1003.
[3] Brunelli C, Amici C, Angelini M, et al. The non-steroidal anti-inflammatory drug indomethacin activates the eIF2alpha kinase PKR, causing a translational block in human colorectal cancer cells[J]. Biochem J, 2012, 443(2): 379-386.
[4] Brady R R, Loveridge C J, Dunlop M G, et al. C-Src dependency of NSAID-induced effects on NF-kappaB-mediated apoptosis in colorectal cancer cells[J]. Carcinogenesis, 2011, 32(7): 1069-1077.
[5] Jones R. Nonsteroidal anti-inflammatory drug prescribing: past, present and future[J]. Am J Med, 2001, 110(1A): 4S-7S.
[6] Laine L. Approaches to nonsteroidal anti-inflammatory drug use in the high-risk patient[J]. Gastroenterology, 2001, 120(3): 594-606.
[7] Allison M C, Howatson A G, Torrance C J, et al. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs[J]. N Engl J Med, 1992, 327(11): 749-754.
[8] Fries J F, Williams C A, Bloch D A, et al. Nonsteroidal anti-inflammatory drug-associated gastropathy: incidence and risk factor models[J]. Am J Med, 1991, 91(3): 213-222.
[9] Dubois R W, Melmed G Y, Henning J M, et al. Risk of Upper Gastrointestinal Injury and Events in Patients Treated With Cyclooxygenase (COX)-1/COX-2 Nonsteroidal Antiinflammatory Drugs (NSAIDs), COX-2 Selective NSAIDs, and Gastroprotective Cotherapy: An Appraisal of the Literature[J]. J Clin Rheumatol, 2004, 10(4): 178-189.
[10] Takeuchi K, Tanaka A, Hayashi Y, et al. Functional mechanism underlying COX-2 expression following administration of indomethacin in rat stomachs: importance of gastric hypermotility[J]. Dig Dis Sci, 2004, 49(2): 180-187.
[11] Takeuchi K, Tanaka A, Hayashi Y, et al. COX inhibition and NSAID-induced gastric damage-roles in various pathogenic events[J]. Curr Top Med Chem, 2005, 5(5): 475-486.
[12] Banerjee D, Bhattacharya S, Bandyopadhyay S K, et al. Biochemical mechanism of healing activity of the natural phenolic, allylpyrocatechol against indomethacin-induced gastric ulceration in mice[J]. Dig Dis Sci, 2008, 53(11): 2868-2877.
[13] Brzozowski T, Tarnawski A, Hollander D, et al. Comparison of prostaglandin and cimetidine in protection of isolated gastric glands against indomethacin injury[J]. J Physiol Pharmacol, 2005, 56 Suppl 5: 75-88.
[14] Nagano Y, Matsui H, Muramatsu M, et al. Rebamipide significantly inhibits indomethacin-induced mitochondrial damage, lipid peroxidation, and apoptosis in gastric epithelial RGM-1 cells[J]. Dig Dis Sci, 2005, 50 Suppl 1: S76-83.
[15] Yoshikawa T, Naito Y, Kishi A, et al. Role of active oxygen, lipid peroxidation, and antioxidants in the pathogenesis of gastric mucosal injury induced by indomethacin in rats[J]. Gut, 1993, 34(6): 732-737.
[16] Chiou S K, Mandayam S. NSAIDs enhance proteasomic degradation of survivin, a mechanism of gastric epithelial cell injury and apoptosis[J]. Biochem Pharmacol, 2007, 74(10): 1485-95.
[17] Nishida T, Yabe Y, Fu H Y, et al. Geranylgeranylacetone induces cyclooxygenase-2 expression in cultured rat gastric epithelial cells through NF-kappaB[J]. Dig Dis Sci, 2007, 52(8): 1890-1896.
[18] Okazaki M, Shimizu I, Ishikawa M, et al. Gastric mucosal levels of prostaglandins and leukotrienes in patients with gastric ulcer after treatment with rabeprazole in comparison to treatment with ranitidine[J]. J Med Invest, 2007, 54(1-2): 83-90.
[19] Skoczylas T, Sarosiek I, Sostarich S, et al. Significant enhancement of gastric mucin content after rabeprazole administration: its potential clinical significance in acid-related disorders[J]. Dig Dis Sci, 2003, 48(2): 322-328.
[20] Ushijima H, Tanaka K, Takeda M, et al. Geranylgeranylacetone protects membranes against nonsteroidal anti-inflammatory drugs[J]. Mol Pharmacol, 2005, 68(4): 1156-1161.
[21] Ohta Y, Kobayashi T, Inui K, et al. Preventive effect of teprenone on acute gastric mucosal lesion progression in compound 48/80-treated rats[J]. Eur J Pharmacol, 2004, 487(1-3): 223-232.
[22] Dekigai H, Nakamura H, Bai J, et al. Geranylgeranylacetone promotes induction and secretion of thioredoxin in gastric mucosal cells and peripheral blood lymphocytes[J]. Free Radic Res, 2001, 35(1): 23-30.
[23] Suemasu S, Tanaka K, Namba T, et al. A role for HSP70 in protecting against indomethacin-induced gastric lesions[J]. J Biol Chem, 2009, 284(29): 19705-19715.
[24] Guth PH, Aures D, Paulsen G. Topical aspirin plus HCl gastric lesions in the rat: cytoprotective effect of prostaglandin, cimetidine, and probanthine[J]. Gastroenterology, 1979, 76(1): 88-93.
[25] Shimizu M, Saitoh Y, Itoh H. Immunohistochemical staining of Ha ras oncogene product in normal, benign, and malignant human pancreatic tissue[J]. Hum Pathol, 1990, 21(6): 607-612.
[26] Li C Q, Xie X J, Yu T, et al. Classification of inflammation activity in ulcerative colitis by confocal laser endomicroscopy[J]. Am J Gastroenterol, 2010, 105(6): 1391-1396.
[27] Anderson J M, Van Itallie C M. Tight junctions and the molecular basis for regulation of paracellular permeability[J]. Am J Physiol, 1995, 269(4 Pt 1): G467-G475.
[1] ZHOU Xiaoyan, LI Ming, GUO Jing, ZUO Xiuli, LI Yanqing. Mucus fills the intestinal epithelial gaps and maintains the barrier function [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(12): 62-66,80.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd