Pro-Apoptotic Effects of Tepoxalin, a Cyclooxygenase/Lipoxygenase Dual Inhibitor, on Canine Synovial Fibroblasts

Journal of Veterinary Medical Science

Kenji HOSOYA¹  Masahiro OKUMURA¹  Namgil OH¹  Takafumi SUNAGA¹  Satoshi TAKAGI¹ 

[1] 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

关键词: apoptosis;    canine;    osteoarthritis;    synoviocytes;    tepoxalin;   

DOI  :  10.1292/jvms.11-0435

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(31)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.

【 授权许可】

Unknown