Effect of thromboxane A2 and leukotriene C4 inhibitors on the experimentally induced gastric lesions in the rat.
Effects of OKY-046, a thromboxane synthetase inhibitor; BM 13.177, a thromboxane A2-receptor antagonist and FPL 55712, a leukotriene antagonist have been studied on gastric lesions induced by necrotizing agents (80% ethanol, 0.6 M HCl, 0.2 M NaOH, 25% NaCl and 100 mM sodium taurocholate), aspirin, indomethacin, reserpine and hypothermic restraint stress in rats. Ro 22-6923, a synthetic trimethyl prostanoid has been used for comparison. OKY-046, FPL 55712 and Ro 22-6923 produced dose dependent inhibition of gastric lesions induced by necrotizing agents and reduced the severity of aspirin, indomethacin, reserpine and hypothermic restraint stress induced lesions. BM 13.177 was not found effective against any of the models used in this study. These observations indicate towards the role of thromboxane A2 and leukotriene C4 in the genesis of gastric lesions induced by different methods. FPL 55712 required considerably lower doses than those of OKY-046 to display its protective effects in these models. Further studies on the levels of thromboxane A2 and leukotriene C4 in the gastric mucosa, are suggested to substantiate these observations.
Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
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Tariq
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Ageel
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000037:antagonists & inhibitors*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*; D013449:Sulfonamides / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
D000897:Anti-Ulcer Agents; D002867:Chromones; D005343:Fibrinolytic Agents; D008689:Methacrylates; D011459:Prostaglandins E, Synthetic; D013189:SRS-A; D013449:Sulfonamides; D013928:Thromboxane A2; C040624:sulotroban; C044129:Ro 22-6923; C006312:FPL 55712; C034364:ozagrel