Source:http://linkedlifedata.com/resource/pubmed/id/10424717
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
1999-9-22
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| pubmed:abstractText |
Endothelin-1 (ET-1), nitric oxide, and cytokines are recognized mediators of the inflammatory processes associated with gastric mucosal injury. In this study, we investigated mucosal expression of ET-1, interleukin-4 (IL-4), and the activity of constitutive nitric oxide synthase (cNOS) during indomethacin-induced gastric mucosal injury, and evaluated the effect of antiulcer agents on this process. The experiments were conducted with groups of rats pretreated intragastrically with ranitidine (100 mg/kg), ebrotidine (100 mg/kg), sulglycotide (200 mg/kg) or vehicle, followed 30 min later by an intragastric dose of indomethacin (60 mg/kg). The animals were killed 2 h later and their mucosal tissue subjected to macroscopic damage assessment and the measurements of epithelial cell apoptosis, ET-1, IL-4, and cNOS. In the absence of antiulcer agents, indomethacin caused multiple hemorrhagic lesions and extensive epithelial cell apoptosis, accompanied by a 20.7% reduction in IL-4, a 3.1-fold increase in mucosal expression of ET-1 and a 4.2-fold decline in cNOS. Pretreatment with H2-receptor antagonist, ranitidine produced a 15.7% reduction in the mucosal damage caused by indomethacin, 29.5% decrease in epithelial cell apoptosis and a 19.6% reduction in ET-1, while the expression of IL-4 increased by 10.8% and that of cNOS showed a 2-fold increase. The H2-blocker, ebrotidine, also known for its gastroprotective effects, reduced the indomethacin-induced lesions by 90.2%, epithelial cell apoptosis decreased by 61% and ET-1 showed a 58.2% decline, while IL-4 increased by 30.6% and that of cNOS showed a 3.1-fold increase. Pretreatment with gastroprotective agent, sulglycotide, led to a 51.2% reduction in the extent of mucosal damage caused by indomethacin, a 43.9% decrease in apoptosis, and a 63.5% decrease in ET-1, while the expression of cNOS increased by 3.4-fold and the level of IL-4 showed a 32.2% increase. The results suggest that an increase in vasoconstrictive ET-1 level combined with a decrease in regulatory cytokine, IL-4, and a loss of compensatory action by cNOS may be responsible for gastric mucosal injury caused by indomethacin. Our findings also point to a value of ebrotidine and sulglycotide in countering the untoward gastrointestinal side effects of NSAID therapy.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Ulcer Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Benzenesulfonates,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Indomethacin,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type III,
http://linkedlifedata.com/resource/pubmed/chemical/Nos3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Ranitidine,
http://linkedlifedata.com/resource/pubmed/chemical/Sialoglycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/ebrotidine,
http://linkedlifedata.com/resource/pubmed/chemical/sulglicotide
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0867-5910
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
50
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
197-210
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| pubmed:dateRevised |
2005-11-17
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| pubmed:meshHeading |
pubmed-meshheading:10424717-Animals,
pubmed-meshheading:10424717-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:10424717-Anti-Ulcer Agents,
pubmed-meshheading:10424717-Apoptosis,
pubmed-meshheading:10424717-Benzenesulfonates,
pubmed-meshheading:10424717-Endothelin-1,
pubmed-meshheading:10424717-Gastric Mucosa,
pubmed-meshheading:10424717-Indomethacin,
pubmed-meshheading:10424717-Interleukin-4,
pubmed-meshheading:10424717-Nitric Oxide Synthase,
pubmed-meshheading:10424717-Nitric Oxide Synthase Type III,
pubmed-meshheading:10424717-Ranitidine,
pubmed-meshheading:10424717-Rats,
pubmed-meshheading:10424717-Rats, Sprague-Dawley,
pubmed-meshheading:10424717-Sialoglycoproteins,
pubmed-meshheading:10424717-Stomach Ulcer,
pubmed-meshheading:10424717-Thiazoles
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| pubmed:year |
1999
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| pubmed:articleTitle |
Endothelin-1, interleukin-4 and nitric oxide synthase modulators of gastric mucosal injury by indomethacin: effect of antiulcer agents.
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| pubmed:affiliation |
Research Center, University of Medicine and Dentistry of New Jersey, Newark 07103-2400, USA.
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| pubmed:publicationType |
Journal Article
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