title: Effect of etodolac on prostaglandin E2 biosynthesis, active oxygen generation and bradykinin formation.
abstract: The inhibitory actions of etodolac on prostaglandin (PG) E2 biosynthesis, active oxygen generation and bradykinin formation were compared with those of indomethacin, diclofenac Na, piroxicam, naproxen, ketoprofen and aspirin. The inhibitory action (IC50 5.35 x 10(-8) M) of etodolac on PGE2 biosynthesis in rabbit articular chondrocytes stimulated by interleukin-1 (IL-1) beta was about 1/5 that of indomethacin. The inhibitory action of etodolac on spontaneous PGE2 biosynthesis in rabbit gastric epithelial cells (RGEs) (IC50 2.27 x 10(-5) M) and Madin-Darby canine kidney cells (MDCKs) (IC50 4.54 x 10(-7) M) was much less than that in rabbit articular chondrocytes stimulated by IL-1 beta and about 1/19 and 1/9 that of indomethacin in rabbit gastric epithelial cells (RGEs) and Madin-Darby canine kidney cells (MDCKs), respectively. The inhibitory action of etodolac on active oxygen generation was similar to that of indomethacin and piroxicam, and more potent than that of naproxen, ketoprofen and aspirin. The inhibitory action of etodolac on bradykinin formation was the most potent among the seven anti-inflammatory drugs tested. Both etodolac and bromelain inhibited the inflammatory pain in concanavalin A-treated paws of rats in a dose-dependent manner, but indomethacin did not. These results indicate that etodolac is an anti-inflammatory drug which suppress IL-1 beta-stimulated PGE2 biosynthesis in rabbit articular chondrocytes, active oxygen generation and bradykinin formation. It has less suppressive action against spontaneous PGE2 biosynthesis in RGEs and MDCKs. Thus, etodolac is considered to be a safe anti-inflammatory drug for clinical use.
authors.affiliation: Research Laboratories, Nippon Shinyaku Co. Ltd., Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.forename: A
authors.initials: A
authors.lastname: Motonaga
authors.forename: J
authors.initials: J
authors.lastname: Dainaka
authors.forename: T
authors.initials: T
authors.lastname: Nishimura
authors.forename: H
authors.initials: H
authors.lastname: Hashii
authors.forename: K
authors.initials: K
authors.lastname: Yamate
authors.forename: F
authors.initials: F
authors.lastname: Ueda
authors.forename: K
authors.initials: K
authors.lastname: Kimura
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001920:Bradykinin / Q000096:biosynthesis*; D001963:Bromelains / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D003208:Concanavalin A / Q000633:toxicity; D003864:Depression, Chemical; D004008:Diclofenac / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D004285:Dogs; D017308:Etodolac / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007660:Ketoprofen / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D009288:Naproxen / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010894:Piroxicam / Q000494:pharmacology; D011817:Rabbits; D051381:Rats
chemical_list: D007375:Interleukin-1; D003208:Concanavalin A; D010894:Piroxicam; D004008:Diclofenac; D017308:Etodolac; D009288:Naproxen; D001963:Bromelains; D007660:Ketoprofen; D015232:Dinoprostone; D001241:Aspirin; D010100:Oxygen; D001920:Bradykinin; D007213:Indomethacin