Differential Effect of Benexate Hydrochloride Betadex on Prostaglandin Levels in Stomach and Inflammatory Site in Rats

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We compared the effects of an anti-ulcer agent, benexate hydrochloride betadex (BHB), on prostaglandin (PG) levels in gastric tissue and inflammatory exudate in untreated and indomethacintreated rats. BHB (100, 300 and 1000 mg/kg, p. o.) showed dose-dependent inhibition of gastric mucosal lesions induced by indomethacin (30 mg/kg, p. o.). Sustained decrease of PGS (PGE2 and 6-keto-PGF1α) in the gastric wall was observed from 0.5 to 6 hr after indomethacin treatment. BHB (300 and 1000 mg/kg) dose-dependently led to recovery of the indomethacin-induced decrease of gastric PGS at 1 and 6 hr after dosing. It did not antagonize the indomethacin-induced decrease of PG levels in the pleural exudate of carrageenin pleurisy nor did it affect the anti-inflammatory effects of indomethacin. BHB (100 to 1000 mg/kg) alone increased gastric PGE2 by 61% to 113%, while it decreased PGE2 levels in the pleural exudate by 9% to 71% at 6 hr after dosing. These results suggest that sustained increase of gastric PGE2 by BHB could be responsible for protection against indomethacin-induced gastric mucosal lesions and that BHB is a suitable anti-ulcer agent for NSAIDs without compromising their anti-inflammatory effects.
社団法人日本薬理学会の論文