Differential effect of benexate hydrochloride betadex on prostaglandin levels in stomach and inflammatory site in rats.
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-PGF(1alpha)) 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.
Division of Pharmacology, Discovery Research Laboratories II, Shionogi & Co., Ltd., Osaka, Japan.
Y
Y
Hori
K
K
Odaguchi
H
H
Jyoyama
K
K
Yasui
T
T
Mizui
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002351:Carrageenan; D015232:Dinoprostone / Q000378:metabolism; D005122:Exudates and Transudates / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D007213:Indomethacin; D008297:Male; D010998:Pleurisy / Q000139:chemically induced / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D013270:Stomach / Q000187:drug effects*; D013272:Stomach Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D001565:Benzoates; D006146:Guanidines; D011453:Prostaglandins; D015121:6-Ketoprostaglandin F1 alpha; D002351:Carrageenan; D015232:Dinoprostone; C057164:benexate; D007213:Indomethacin