Masaki M, Matsushita M, Wakitani K
Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka.
Inflamm Res. 1998 Apr;47(4):187-92. doi: 10.1007/s000110050316.
To investigate the effect of JTE-522, a novel selective prostaglandin H synthase (PGHS)-2 inhibitor, on adjuvant-induced arthritis and bone changes.
Male Lewis rats at 8 weeks old were immunized with heat-killed mycobacteria.
JTE-522 (0.1-30 mg/kg) and indomethacin (0.1-3 mg/kg) were administered orally once-daily after immunization.
Paw swelling, bone changes in arthritic paws and vertebrae, urinary levels of deoxypyridinoline and pyridinium crosslinks, and the incidence of gastric lesions were determined in arthritic rats.
JTE-522 (from 0.3 mg/kg) suppressed the development of paw swelling, and also reduced bone damage (score and bone mineral density) in arthritic paws and the urinary excretion of deoxypyridinoline and pyridinium crosslinks. However, JTE-522 did not cause gastric lesions even at 30 mg/kg in arthritic rats.
These results suggest that JTE-522 possesses potent anti-arthritic activities and suppressive activity on inflammatory bone resorption without gastric side effects.
研究新型选择性前列腺素H合成酶（PGHS）-2抑制剂JTE-522对佐剂诱导性关节炎和骨骼变化的影响。
8周龄雄性Lewis大鼠用热灭活分枝杆菌免疫。
免疫后，JTE-522（0.1 - 30毫克/千克）和吲哚美辛（0.1 - 3毫克/千克）每日口服一次。
测定关节炎大鼠的爪肿胀、关节炎爪和椎骨的骨骼变化、脱氧吡啶啉和吡啶交联物的尿水平以及胃部病变的发生率。
JTE-522（从0.3毫克/千克起）抑制爪肿胀的发展，还减少了关节炎爪的骨损伤（评分和骨矿物质密度）以及脱氧吡啶啉和吡啶交联物的尿排泄。然而，在关节炎大鼠中，即使剂量为30毫克/千克，JTE-522也未引起胃部病变。
这些结果表明，JTE-522具有强大的抗关节炎活性和对炎症性骨吸收的抑制活性，且无胃部副作用。
