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

Steven Hugenberg, K. D. Brandt, C. A. Cole

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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 μM 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 activiry 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.

Original languageEnglish
Pages (from-to)2128-2133
Number of pages6
JournalJournal of Rheumatology
Volume20
Issue number12
StatePublished - 1993

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Sodium Salicylate
Glucuronosyltransferase
Chondroitin Sulfates
Ibuprofen
Chondrocytes
Salicylates
Aspirin
Uridine Diphosphate Glucose Dehydrogenase
Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
Enzymes
Hexoses
Synovial Fluid
Articular Cartilage
Proteoglycans
Cartilage
Anti-Inflammatory Agents
Joints
Pharmaceutical Preparations

Keywords

  • chondroitin sulfate
  • glucuronosyltransferase
  • glutamine-fructose-6-phosphate aminotransferase
  • ibuprofen
  • salicylate
  • UDP-glucose dehydrogenase

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Effect of sodium salicylate, aspirin, and ibuprofen on enzymes required by the chondrocyte for synthesis of chondroitin sulfate. / Hugenberg, Steven; Brandt, K. D.; Cole, C. A.

In: Journal of Rheumatology, Vol. 20, No. 12, 1993, p. 2128-2133.

Research output: Contribution to journalArticle

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abstract = "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 μM 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 activiry 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.",
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N2 - 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 μM 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 activiry 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.

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