title: Pro-apoptotic effects of tepoxalin, a cyclooxygenase/lipoxygenase dual inhibitor, on canine synovial fibroblasts.
abstract: Canine osteoarthritis occurs frequently and causes secondary synovitis. Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is one of the major therapeutic options for pain management of joint diseases. Tepoxalin has an unique property as an NSAIDs that suppresses both cyclooxygenase and lipoxygenase. The purpose of this study was to evaluate antiproliferative effects of tepoxalin on cultured canine synovial cells. Cytotoxic effects of tepoxalin, carprofen, meloxicam and AA-861 on cultured canine synoviocytes were evaluated by MTT colorimetric assay. Apoptosis was detected by morphological observations with Giemsa or annexin V/Hoechst 33342 staining and by the inhibition of caspase-3 activity with N-Ac-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO). Cytotoxic effects of tepoxalin were evident in comparison with the effects of carprofen or meloxicam. The same tendency of cytotoxicity was observed when 5-lipoxygenase was inhibited by AA-861. The morphological findings and contradictory effects of Ac-DEVD-CHO with regard to the cytotoxicity proved the proapoptotic effects of tepoxalin. In conclusion, tepoxalin might control osteoarthritic synovitis by inducing apoptosis in proliferating synoviocytes, while most NSAIDs that selectively inhibit cyclooxygenase-2 most likely would not suppress synovial proliferation.
authors.affiliation: Laboratory of Veterinary Surgery, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Sunaga
authors.forename: Namgil
authors.initials: N
authors.lastname: Oh
authors.forename: Kenji
authors.initials: K
authors.lastname: Hosoya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takagi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okumura
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001399:Azure Stains; D001562:Benzimidazoles; D016227:Benzoquinones / Q000633:toxicity; D002227:Carbazoles / Q000633:toxicity; D002478:Cells, Cultured; D003124:Colorimetry; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D004285:Dogs; D005347:Fibroblasts / Q000187:drug effects*; D016859:Lipoxygenase Inhibitors / Q000633:toxicity*; D000077239:Meloxicam; D011720:Pyrazoles / Q000633:toxicity*; D013582:Synovial Fluid / Q000166:cytology*; D013778:Tetrazolium Salts; D013843:Thiazines / Q000633:toxicity; D013844:Thiazoles / Q000633:toxicity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001399:Azure Stains; D001562:Benzimidazoles; D016227:Benzoquinones; D002227:Carbazoles; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D013778:Tetrazolium Salts; D013843:Thiazines; D013844:Thiazoles; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; C022616:thiazolyl blue; C007005:carprofen; C017807:bisbenzimide ethoxide trihydrochloride; C073135:tepoxalin; D000077239:Meloxicam