Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage.

Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage. Abstract Text:

K Takeuchi,A Tanaka,R Ohno,A Yokota,K Takeuchi,A Tanaka,R Ohno,A Yokota,

Nonsteroidal antiinflammatory drugs (NSAIDs) such as indomethacin decrease mucosal PGE(2) production by inhibiting cyclooxygenase (COX) activity and produce damage in the small intestine. The development of intestinal lesions as induced by indomethacin was accompanied by increases in intestinal motility, enterobacterial invasion, and myeloperoxidase (MPO) as well as inducible nitric oxide synthase (iNOS) activity, together with the up-regulation of COX-2 and iNOS mRNA expression. Neither the selective COX-1 inhibitor, SC-560, nor the selective COX-2 inhibitor, rofecoxib, alone caused intestinal damage, but their combined administration produced lesions. SC-560, but not rofecoxib, caused intestinal hypermotility, bacterial invasion and the expression of COX-2 as well as iNOS mRNAs, yet the iNOS and MPO activity was increased only when rofecoxib was administered together with SC-560. Although SC-560 inhibited the PG production, the level of PGE(2) was recovered, in a rofecoxib-dependent manner. The intestinal hypermotility response to indomethacin was prevented by both 16,16-dimethyl PGE(2) and atropine but not ampicillin, yet all these agents inhibited not only the bacterial invasion but also the expression of COX-2 as well as the iNOS activity in the intestinal mucosa following indomethacin treatment, resulting in preventing the intestinal lesions. These results suggest that inhibition of COX-1, despite causing intestinal hypermotility, bacterial invasion and iNOS expression, up-regulates the expression of COX-2, and the PGE(2) derived from COX-2 counteracts deleterious events caused by COX-1 inhibition and maintains the mucosal integrity. These sequences of events explain why intestinal damage occurs when both COX-1 and COX-2 are inhibited.

Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage. Publishing Authors By Initials

K Takeuchi,A Tanaka,R Ohno,A Yokota,K Takeuchi,A Tanaka,R Ohno,A Yokota,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of physiology and pharmacology : an offici

VOLUME: 54 Suppl 4

Page Numbers: 165-82

Journal Abbreviation: J. Physiol. Pharmacol.

ISSN: 0867-5910

DAY: 12

MONTH: Dec

YEAR: 2003

Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9114501

Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage.

AFFILIATION: Department of Pharmacology and Experimental Therapeutics Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan. takeuchi@mb.kyoto-phu.ac.jp

Country: Poland

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: J Physiol Pharmacol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage Related Publications

• Access to treatment and care associated with HIV infection among members of AIDS support groups in Thailand.
• Amphibacillus sediminis sp. nov., an endospore-forming bacterium isolated from lake sediment in Japan.
• Anesthetic management of simultaneous coronary artery bypass grafting and cardiac pheochromocytoma resection under cardiopulmonary bypass.
• Cerebral endothelial damage after severe head injury.
• Continuous spectrophotometric assays for three regulatory enzymes of the arginine biosynthetic pathway.
• Diversity and mechanisms of alkali tolerance in lactobacilli.
• Effects of surgical holes in mouse tibiae on bone formation induced by knee loading.
• Efficacy of plasma exchange therapy for Kawasaki disease intractable to intravenous gamma-globulin.
• Enzymatic characterization of 5-methylthioribose 1-phosphate isomerase from Bacillus subtilis.
• Facilitation of perceptual filling-in for spatio-temporal frequency of dynamic textures.
• Forced expression of Id2 in fetal thymic T cell progenitors allows some of their progeny to adopt NK cell fate.
• Frequency-dependent enhancement of bone formation in murine tibiae and femora with knee loading.
• Halobacillus faecis sp. nov., a spore-forming bacterium isolated from a mangrove area on Ishigaki Island, Japan.
• Henoch-Schonlein purpura presenting duodenal involvement similar to superior mesenteric artery syndrome in a girl.
• Homozygous deletion scanning of the lung cancer genome at a 100-kb resolution.
• In vitro glucuronidation of estradiol-17beta by microsomes prepared using liver biopsy specimens from dairy cows.
• Influence of Small Eye Movement on Perceptual Filling-in Time.
• Knee loading accelerates bone healing in mice.
• Knee loading dynamically alters intramedullary pressure in mouse femora.
• Knee-loading modality drives molecular transport in mouse femur.
• Localization of a human lung adenocarcinoma susceptibility locus, possibly syntenic to the mouse Pas1 locus, in the vicinity of the D12S1034 locus on chromosome 12p11.2-p12.1.
• Long-term follow-up of busulfan, etoposide, and nimustine hydrochloride (ACNU) or melphalan as conditioning regimens for childhood acute leukemia and lymphoma.
• Modelling and identification of transcription-factor binding motifs in human chondrogenesis.
• Pelagicoccus croceus sp. nov., a novel marine member of the family Puniceicoccaceae within the phylum 'Verrucomicrobia' isolated from seagrass.
• Purification and characterization of alkaline phosphatase in cultured rat liver cells.
• Role of COX inhibition in pathogenesis of NSAID-induced small intestinal damage.
• Rubritalea spongiae sp. nov. and Rubritalea tangerina sp. nov., two carotenoid- and squalene-producing marine bacteria of the family Verrucomicrobiaceae within the phylum 'Verrucomicrobia', isolated from marine animals.
• Stress to endoplasmic reticulum of mouse osteoblasts induces apoptosis and transcriptional activation for bone remodeling.
• Toxic epidermal necrolysis in a child successfully treated with cyclosporin A and methylprednisolone.
• [Gene therapy of ALS with short interfering RNA]