Inhibitory effects of JTE-522, a novel prostaglandin H synthase-2 inhibitor, on adjuvant-induced arthritis and bone changes in rats.
OBJECTIVE
To investigate the effect of JTE-522, a novel selective prostaglandin H synthase (PGHS)-2 inhibitor, on adjuvant-induced arthritis and bone changes.


METHODS
Male Lewis rats at 8 weeks old were immunized with heat-killed mycobacteria.


METHODS
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.
Masaki
M
M
Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka.
Matsushita
M
M
Wakitani
K
K
D000284:Administration, Oral; D000596:Amino Acids / Q000652:urine; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use* / Q000633:toxicity; D001169:Arthritis, Experimental / Q000209:etiology / Q000517:prevention & control* / Q000652:urine; D001557:Benzenesulfonates / Q000627:therapeutic use* / Q000633:toxicity; D015519:Bone Density / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use* / Q000633:toxicity; D006614:Hindlimb / Q000000981:diagnostic imaging; D007213:Indomethacin / Q000627:therapeutic use / Q000633:toxicity; D008297:Male; D010080:Oxazoles / Q000627:therapeutic use* / Q000633:toxicity; D011726:Pyridinium Compounds / Q000652:urine; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D000096926:Benzenesulfonamides
D000596:Amino Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001557:Benzenesulfonates; D016861:Cyclooxygenase Inhibitors; D007213:Indomethacin; D010080:Oxazoles; D011726:Pyridinium Compounds; C110453:4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamide; D000096926:Benzenesulfonamides; C036020:deoxypyridinoline