Gastric toxicity and prostaglandin content in rats dosed with two chemically similar, nonsteroidal anti-inflammatory agents.

Abstract	Two chemically similar nonsteroidal anti-inflammatory drugs, orpanoxin and F-1067, had almost identical potencies and efficacies as anti-inflammatory (rat paw edema) and analgesic (mouse writhing) agents, but differed markedly in gastrotoxicity. Orpanoxin alone aggravated stomach lesions in rats subjected to pylorus ligation and failed to protect stomachs of rats challenged with indomethacin. The compounds did not differ in their in vitro enzyme inhibition effects, both failing to inhibit 5- and 15-lipoxygenase and both inhibiting prostaglandin synthetase. Extraction of prostaglandins from the gastric mucosa of pylorus-ligated rats revealed, however, that the safer F-1067 depleted prostaglandin 6-keto-F1 alpha less and increased prostaglandin E2 much more than did orpanoxin. A possible causality is suggested.
Authors	R R Brooks, T J Moorehead, S F Pong
Journal	Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) (Proc Soc Exp Biol Med) Vol. 202 Issue 2 Pg. 233-8 (Feb 1993) ISSN: 0037-9727 [Print] United States
PMID	8424114 (Publication Type: Comparative Study, Journal Article)
Chemical References	Anti-Inflammatory Agents, Non-Steroidal Cyclooxygenase Inhibitors Furans Lipoxygenase Inhibitors Propionates benoxaprofen 5-(4-chlorophenyl)-2-furanpropionic acid 6-Ketoprostaglandin F1 alpha orpanoxin Dinoprostone Indomethacin
Topics	6-Ketoprostaglandin F1 alpha (metabolism) Animals Anti-Inflammatory Agents, Non-Steroidal (pharmacology, toxicity) Cyclooxygenase Inhibitors (pharmacology) Dinoprostone (metabolism) Female Furans (pharmacology, toxicity) Gastric Mucosa (drug effects, metabolism, pathology) Indomethacin (pharmacology) Inflammation Lipoxygenase Inhibitors Male Plants (enzymology) Propionates (pharmacology, toxicity) Rats Rats, Sprague-Dawley Rats, Wistar Seminal Vesicles (enzymology) Sheep Stomach (drug effects, pathology) Structure-Activity Relationship

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