Temporal relationships of the anti-inflammatory effect of etodolac in the adjuvant arthritic rat.
Using the curative model of adjuvant arthritis, adult male Sprague-Dawley rats were treated with vehicle or etodolac (1, 3, and 8 mg/kg/day, po) for 9 days. Rats were sacrificed after 1, 2, 4, or 9 daily doses, and paw volume, PGE2 concentrations, and N-acetyl-beta-D-glucosaminidase (NAG) activity were determined in the left adjuvant-injected hindpaws. All three doses of etodolac caused a significant decrease in PGE2 concentrations after the first dose, and the decreases persisted for 2, 4, and 9 days of treatment, respectively. In rats given four daily doses of 3 and 8 mg/kg/day of etodolac, the paw volume was significantly decreased by about 50%, compared with that of the arthritic controls. A significant decrease in NAG activity was observed only after nine daily doses of 8 mg/kg/day etodolac. The sequence of anti-inflammatory events manifested following etodolac treatment would appear to be an initial inhibition of PGE2 synthesis, followed by resorption of fluid, and then by a reduction in macrophage infiltration.
Lee
D K
DK
Department of Biochemistry, Ayerst Laboratories Research, Inc., Princeton, New Jersey 08543-8000.
Chau
T T
TT
Weichman
B M
BM
Wooley
P H
PH
D000085:Acetates / Q000494:pharmacology*; D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001168:Arthritis / Q000188:drug therapy*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015232:Dinoprostone; D004487:Edema / Q000503:physiopathology; D017308:Etodolac; D006614:Hindlimb; D008297:Male; D011458:Prostaglandins E / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000085:Acetates; D000893:Anti-Inflammatory Agents; D011458:Prostaglandins E; D017308:Etodolac; D000118:Acetylglucosaminidase; D015232:Dinoprostone