Role of prostaglandins generated by cyclooxygenase-1 and cyclooxygenase-2 in healing of ischemia-reperfusion-induced gastric lesions.
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.
Brzozowski
T
T
Department of Physiology and Pathomorphology, Jagiellonian University School of Medicine, ul. Grzegórzecka 16, 31-531, Cracow, Poland.
Konturek
P C
PC
Konturek
S J
SJ
Sliwowski
Z
Z
Drozdowicz
D
D
Stachura
J
J
Pajdo
R
R
Hahn
E G
EG
D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000473:pathology*; D005755:Gastrins / Q000097:blood; D015971:Gene Expression Regulation, Enzymologic; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000097:blood; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology; D000077239:Meloxicam; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000150:complications* / Q000503:physiopathology; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology; D013276:Stomach Ulcer / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D013449:Sulfonamides / Q000494:pharmacology; D013450:Sulfones; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005755:Gastrins; D007375:Interleukin-1; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D009578:Nitrobenzenes; D011453:Prostaglandins; D012333:RNA, Messenger; D013267:Stilbenes; D013449:Sulfonamides; D013450:Sulfones; D013843:Thiazines; D013844:Thiazoles; C116926:rofecoxib; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D015232:Dinoprostone; D000077185:Resveratrol; D000077239:Meloxicam; D007213:Indomethacin