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Role of prostaglandins generated by cyclooxygenase-1 and cyclooxygenase-2 in healing of ischemia-reperfusion-induced gastric lesions.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 1999 Nov 26; Vol. 385 (1), pp. 47-61. - Publication Year :
- 1999
-
Abstract
- In this study, ischemia-reperfusion produced in rats by clamping the celiac artery for 0.5 h followed by 1 h of reperfusion was used to develop a new model of superficial gastric erosions progressing to deeper ulcers. Ischemia alone resulted in an immediate fall in gastric blood flow but no gross mucosal lesions were observed. When ischemia was followed by reperfusion, gastric erosive lesions occurred, reached a maximum at 12 h and then declined after 24 h. These acute erosions progressed into deeper lesions 24 h after ischemia-reperfusion and reached a peak after 3 days. Gastric blood flow and the mucosal generation of prostaglandin E(2) were significantly suppressed immediately following ischemia-reperfusion, but with the healing of deeper gastric ulcers, both gastric blood flow and prostaglandin E(2) generation were gradually restored. Cyclooxygenase-1 mRNA was detected by reverse transcription-polymerase chain reaction in intact gastric mucosa and throughout the recovery of the mucosa from acute ischemia-reperfusion lesions, whereas cyclooxygenase-2 mRNA, was recorded only after ischemia-reperfusion. NS-398 and rofecoxib, selective inhibitors of cyclooxyganase-2, failed to affect prostaglandin E(2) generation in the non-ulcerated gastric mucosa but inhibited it significantly in the ulcer area. The two cyclooxygenase-2 inhibitors as well as resveratrol, a specific cyclooxygenase-1 inhibitor and indomethacin and meloxicam, non-specific inhibitors of cyclooxygenase, augmented acute gastric erosions induced by ischemia-reperfusion and delayed significantly the progression of these lesions into deeper ulcers at each time interval after ischemia-reperfusion. We conclude that prostaglandins generated by both cyclooxygenase-1 and cyclooxygenase-2 contribute to the healing of gastric lesions induced by ischemia-reperfusion.
- Subjects :
- Animals
Cyclooxygenase 1
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors pharmacology
Dinoprostone metabolism
Dinoprostone pharmacology
Disease Models, Animal
Gastric Mucosa blood supply
Gastric Mucosa drug effects
Gastrins blood
Gene Expression Regulation, Enzymologic
Indomethacin pharmacology
Interleukin-1 blood
Isoenzymes genetics
Isoenzymes pharmacology
Lactones pharmacology
Meloxicam
Membrane Proteins
Nitrobenzenes pharmacology
Prostaglandin-Endoperoxide Synthases genetics
Prostaglandin-Endoperoxide Synthases pharmacology
Prostaglandins pharmacology
Prostaglandins physiology
RNA, Messenger genetics
RNA, Messenger metabolism
Rats
Regional Blood Flow drug effects
Reperfusion Injury physiopathology
Resveratrol
Reverse Transcriptase Polymerase Chain Reaction
Stilbenes pharmacology
Stomach Ulcer drug therapy
Stomach Ulcer etiology
Sulfonamides pharmacology
Sulfones
Thiazines pharmacology
Thiazoles pharmacology
Time Factors
Gastric Mucosa pathology
Isoenzymes metabolism
Prostaglandin-Endoperoxide Synthases metabolism
Prostaglandins metabolism
Reperfusion Injury complications
Stomach Ulcer enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 385
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 10594344
- Full Text :
- https://doi.org/10.1016/s0014-2999(99)00681-0