Effect of misoprostol and indomethacin on cyclooxygenase induction and eicosanoid production in carrageenan-induced air pouch inflammation in rats.
Effects of misoprostol, a synthetic prostaglandin E1 (PGE1) analogue, on cyclooxygenase-2 (COX-2) protein level and exudate prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) level were investigated in acute carrageenan-induced air pouch inflammation in rats. Treatment with misoprostol (12.5, 25, and 50 microg/kg) has been started in separated groups, 30 min and 2 days before carrageenan injection and it was given twice a day (total of five doses) by orogastric route. Indomethacin, in doses of 0.5 and 5 mg/kg, and specific COX-2 inhibitor SC-58236, in doses of 5, 10, and 20 mg/kg were given 1 h before carrageenan injection by the orogastric route. Misoprostol increased the levels of PGE2 and COX-2 protein at all doses applied. Despite indomethacin and SC-58236 increased the level of COX-2 protein when they used alone, these drugs partially inhibited misoprostol-induced increase in the level of COX-2 protein. Partial inhibition of misoprostol-induced increase in the level of COX-2 protein by indomethacin or SC-58236 may indicate the modulatory roles of endogenous prostaglandins (PGs, especially, PGE2) on the COX-2 expression.
Buluç
Mesut
M
Department of Pharmacology and Clinical Pharmacology, Medical Faculty of Ankara University, Turkey.
Gürdal
Hakan
H
Melli
Mehmet
M
D000818:Animals; D002351:Carrageenan; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D004338:Drug Combinations; D004790:Enzyme Induction; D005122:Exudates and Transudates / Q000737:chemistry; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism*; D007527:Isoenzymes / Q000096:biosynthesis*; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D016595:Misoprostol / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011720:Pyrazoles; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides; D013929:Thromboxane B2 / Q000096:biosynthesis*; D000096926:Benzenesulfonamides
D002351:Carrageenan; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D004338:Drug Combinations; D007213:Indomethacin; D007527:Isoenzymes; D016595:Misoprostol; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides; D013929:Thromboxane B2; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides