Inhibitory effects of JTE-522, a novel prostaglandin H synthase-2 inhibitor, on adjuvant-induced arthritis and bone changes in rats

Abstract

Objective and Design: To investigate the effect of JTE-522, a novel selective prostaglandin H synthase (PGHS)-2 inhibitor, on adjuvant-induced arthritis and bone changes.¶Subjects: Male Lewis rats at 8 weeks old were immunized with heat-killed mycobacteria.¶Treatment: JTE-522 (0.1–30 mg/kg) and indomethacin (0.1–3 mg/kg) were administered orally once-daily after immunization.¶Methods: 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.¶Results: 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.¶Conclusions: These results suggest that JTE-522 possesses potent anti-arthritic activities and suppressive activity on inflammatory bone resorption without gastric side effects.