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)I and ibuprofen (Ibu) (as the racemic mixtu re and the R- and S-enantiomers) on the activities of 2 enzymes involv ed in the biosynthesis of the hexose components of chondroitin sulfate (CS), i.e., UDP-glucose dehydrogenase (UDP-GD) and glutamine-fructose -6-phosphate-aminotran (GFAT), and of glucuronosyltransferase (GT), an enzyme involved in elongation of the nascent CS chain. Methods. UDP-G D 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. Neit her 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 mu M Ibu). In contrast, GT activity was inhibited by Sal and ASA in a concentration dependent fashion; at 1.0 mM, a concentration c ommonly reached in synovial fluid of patients treated with an antiinfl ammatory 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 v alue. In contrast, a clinically relevant concentration of Ibu had no e ffect on GT activity. Conclusion. Salicylates may suppress cartilage p roteoglycan synthesis by inhibiting GT.