EFFECT OF CARPROFEN ON SULFATED GLYCOSAMINOGLYCAN METABOLISM, PROTEIN-SYNTHESIS, AND PROSTAGLANDIN RELEASE BY CULTURED OSTEOARTHRITIC CANINE CHONDROCYTES
Hp. Benton et al., EFFECT OF CARPROFEN ON SULFATED GLYCOSAMINOGLYCAN METABOLISM, PROTEIN-SYNTHESIS, AND PROSTAGLANDIN RELEASE BY CULTURED OSTEOARTHRITIC CANINE CHONDROCYTES, American journal of veterinary research, 58(3), 1997, pp. 286-292
Objective-To determine whether the nonsteroidal anti-inflammatory drug
carprofen directly influences canine chondrocyte metabolism. Animals-
Cartilage from the femoral heads of 73 dogs undergoing total hip repla
cement. Procedure-Rates of glycosaminoglycan (GAG) synthesis and degra
dation, protein synthesis, cell viability, and prostaglandin release w
ere determined in canine explant cartilage or monolayer canine chondro
cyte cultures in the presence of 0 to 100 mu g of carprofen/ml. Rate o
f GAG synthesis was assessed as incorporation of [S-35]sulfate into ca
rtilage matrix during a 3-hour pulse label. Degradation of cartilage G
AG was assessed as rate of release of [S-35]sulfate from prelabeled ex
plant cultures. Rates of total protein synthesis were assessed as inco
rporation of [S-35]methionine into trichloracetic acid precipitable ma
terial during a 3-hour pulse label. Radiolabeled chondrocyte proteins
were separated by polyacrylamide gel electrophoresis and visualized by
fluorography. Rates of prostaglandin E(2) release were assessed by ra
dioimmunoassay. Results-Carprofen stimulated a significant increase in
the rate of GAG synthesis at concentrations of 1 and 10 mu g/ml, with
no change in total protein synthesis, pattern of new protein synthesi
s, or cell viability. At concentration greater than or equal to 20 mu
g/ml, inhibition of GAG synthesis and total protein synthesis was obse
rved. There was no significant change in rate of release of GAG from c
artilage explants, but potent inhibition of prostaglandin release was
observed. Conclusions-Carprofen has a direct influence on chondrocyte
activity, resulting in changes in rate of production of cartilage matr
ix. Clinical Relevance-In determining the optimal therapeutic dose of
carprofen for arthritic conditions in dogs, it is important to conside
r potential influences on cartilage, as well as anti-inflammatory acti
ons.