Yozo Hori, Kunihiro Odaguchi, Hirokuni Jyoyama, Kiyoshi Yasui and Takuji Mizui
Division of Pharmacology, Discovery Research Laboratories II, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561, Japan
Abstract: 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 indomethacin-treated 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-PGF1alpha) 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 NSAlDs without compromising their anti-inflammatory effects.
Keywords:
Benexate hydrochloride betadex, Gastric mucosa, Indomethacin, Prostaglandin, Pleurisy