2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic-acid and Necrosis

This study demonstrates that the suppression of thromboxane biosynthesis by OKY-1581, a selective inhibitor of thromboxane biosynthesis, prevents dose-dependently taurocholate-induced gastric mucosal necrosis and enhances the cytoprotective effect of low dose of taurocholate against mucosal necrosis by large dose of this agent. In all animals treated with OKY-1581, a decrease in mucosal generation of thromboxane was accompanied by an increased production of PGs probably due to availability of greater amounts of a common substrate in a cyclooxygenase pathway. This study provides direct evidence that gastric mucosa generates thromboxanes which may be involved in the pathogenesis of taurocholate-induced gastric mucosal lesions.

Topics: Animals; Dinoprostone; Epoprostenol; Female; Gastric Mucosa; Indomethacin; Male; Methacrylates; Necrosis; Prostaglandins; Prostaglandins E; Rats; Rats, Inbred Strains; Taurocholic Acid; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes

The effects of a new selective inhibitor of thromboxane biosynthesis, OKY-1581, and a potent inhibitor of cyclooxygenase, indomethacin, on gastric mucosal lesions induced by taurocholate or ethanol and mucosal generation of prostaglandins have been studied in rats. OKY-1581 prevented, dose dependently, the formation of taurocholate- but not ethanol-induced gastric necrosis, and this effect was accompanied by an increase in gastric mucosal generation of prostaglandin E2 and I2-like activity and a reduction in the thromboxane generation during platelet aggregation. OKY-1581 enhanced the cytoprotective action of "mild" irritants such as 5 mM taurocholate against gastric damage by 100 mM taurocholate, whereas indomethacin produced opposite effects. This study indicates: (1) the inhibition of thromboxane biosynthesis results in increased generation of prostaglandins which seems to contribute to the gastric mucosal integrity and, (2) thromboxanes may be involved in the pathogenesis of taurocholate-induced gastric mucosal lesions.

Topics: Animals; Dinoprostone; Epoprostenol; Ethanol; Female; Gastric Mucosa; Indomethacin; Male; Methacrylates; Necrosis; Platelet Aggregation; Prostaglandins; Prostaglandins E; Rats; Rats, Inbred Strains; Taurocholic Acid; Thromboxane-A Synthase; Thromboxanes