Effect of sodium salicylate, aspirin, and ibuprofen on enzymes required by the chondrocyte for synthesis of chondroitin sulfate.

Objective: To examine the effects of sodium salicylate (Sal), aspirin [acetylsalicylic acid (ASA)] and ibuprofen (Ibu) (as the racemic mixture and the R- and S-enantiomers) on the activities of 2 enzymes involved in the biosynthesis of the hexose components of chondroitin sulfate (CS), i.e., UDP-glucose dehydrogenase (UDP-GD) and glutamine-fructose-6-phosphate-aminotransferase (GFAT), and of glucuronosyltransferase (GT), an enzyme involved in elongation of the nascent CS chain.

Methods: UDP-GD and GT were obtained commercially. A homogenate of bovine articular cartilage chondrocytes was employed as a source of GFAT. In each case, enzymatic activity was measured spectrophotometrically.

Results: Neither UDP-GD nor GFAT was inhibited by concentrations of Sal, ASA or Ibu that were achieved clinically in joint tissues (e.g., 1.0 mM Sal and ASA, 170 microM Ibu). In contrast, GT activity was inhibited by Sal and ASA in a concentration dependent fashion; at 1.0 mM, a concentration commonly reached in synovial fluid of patients treated with an antiinflammatory dose of the drug, GT activity in the presence of Sal and ASA was 54% (p = 0.001) and 75% (p = 0.05), respectively, of the control value. In contrast, a clinically relevant concentration of Ibu had no effect on GT activity.

Conclusion: Salicylates may suppress cartilage proteoglycan synthesis by inhibiting GT.