Effect of celecoxib, a cyclooxygenase-2 inhibitor, on the pathophysiology of adjuvant arthritis in rat.
We investigated the efficacy of celecoxib, a specific cyclooxygenase (COX)-2 inhibitor, on arthritic pathophysiology and confirmed its gastric safety in adjuvant-induced arthritis rats. Results were compared with those for loxoprofen, a non-selective COX inhibitor. Arthritis was induced by injection of 1 mg of Mycobacterium butyricum in 50 microl of liquid paraffin into the left footpad of Lewis rats. The drugs were given by twice daily oral administration for 10 days beginning 15 days after adjuvant injection, with celecoxib at 0.01-3 mg/kg/day and loxoprofen at 0.01-3 mg/kg/day. Celecoxib significantly inhibited paw swelling, hyperalgesic response, and joint destruction (radiographic and histopathological findings) in these arthritic rats. These effects of celecoxib were superior to those of loxoprofen. Further, the administration of loxoprofen (3 mg/kg/day) caused significant gastric lesions, whereas celecoxib at the same dose did not. These results suggest that COX-2-mediated prostaglandins may play an important role in the progression of pathophysiology in this model and that celecoxib may be a useful therapeutic agent for the treatment of rheumatoid arthritis, with greater safety than non-selective COX inhibitors.
Noguchi
Masahiro
M
Pharmacology Laboratories Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21, Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan.
Kimoto
Aishi
A
Kobayashi
Seiji
S
Yoshino
Taiji
T
Miyata
Keiji
K
Sasamata
Masao
M
D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006614:Hindlimb; D007596:Joints / Q000473:pathology; D008297:Male; D009161:Mycobacterium; D010146:Pain / Q000209:etiology / Q000517:prevention & control; D010666:Phenylpropionates / Q000009:adverse effects / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D013276:Stomach Ulcer / Q000139:chemically induced; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D010666:Phenylpropionates; D011720:Pyrazoles; D013449:Sulfonamides; C040656:loxoprofen; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib