Synergistic Chondroprotective Effect of α-Tocopherol, Ascorbic Acid, and Selenium as well as Glucosamine and Chondroitin on Oxidant Induced Cell Death and Inhibition of Matrix Metalloproteinase-3—Studies in Cultured Chondrocytes

Autor: Anne-Christi Graeser, Katri Giller, Heike Wiegand, Luca Barella, Christine Boesch Saadatmandi, Gerald Rimbach
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Zdroj: Molecules, Vol 15, Iss 1, Pp 27-39 (2009)
Druh dokumentu: article
ISSN: 1420-3049
DOI: 10.3390/molecules15010027
Popis: Overproduction of reactive oxygen species and impaired antioxidant defence accompanied by chronic inflammatory processes may impair joint health. Pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) stimulate the expression of metalloproteinases which degrade the extracellular matrix. Little is known regarding the potential synergistic effects of natural compounds such as α-tocopherol (α-toc), ascorbic acid (AA) and selenium (Se) on oxidant induced cell death. Furthermore studies regarding the metalloproteinase-3 inhibitory activity of glucosamine sulfate (GS) and chondroitin sulfate (CS) are scarce. Therefore we have studied the effect of α-toc (0.1–2.5 µmol/L), AA (10–50 µmol/L) and Se (1–50 nmol/L) on t-butyl hydroperoxide (t-BHP, 100–500 µmol/L)-induced cell death in SW1353 chondrocytes. Furthermore we have determined the effect of GS and CS alone (100–500 µmol/L each) and in combination on MMP3 mRNA levels and MMP3 secretion in IL-1β stimulated chondrocytes. A combination of α-toc, AA, and Se was more potent in counteracting t-BHP-induced cytotoxicity as compared to the single compounds. Similarly a combination of CS and GS was more effective in inhibiting MMP3 gene expression and secretion than the single components. The inhibition of MMP3 secretion due to GS plus CS was accompanied by a decrease in TNF-α production. Combining natural compounds such as α-toc, AA, and Se as well as GS and CS seems to be a promising strategy to combat oxidative stress and cytokine induced matrix degradation in chondrocytes.
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