title: Synergistic chondroprotective effect of alpha-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.
abstract: Overproduction of reactive oxygen species and impaired antioxidant defence accompanied by chronic inflammatory processes may impair joint health. Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) stimulate the expression of metalloproteinases which degrade the extracellular matrix. Little is known regarding the potential synergistic effects of natural compounds such as alpha-tocopherol (alpha-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 alpha-toc (0.1-2.5 micromol/L), AA (10-50 micromol/L) and Se (1-50 nmol/L) on t-butyl hydroperoxide (t-BHP, 100-500 micromol/L)-induced cell death in SW1353 chondrocytes. Furthermore we have determined the effect of GS and CS alone (100-500 micromol/L each) and in combination on MMP3 mRNA levels and MMP3 secretion in IL-1beta stimulated chondrocytes. A combination of alpha-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-alpha production. Combining natural compounds such as alpha-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.
authors.affiliation: Institute of Human Nutrition and Food Science, Christian Albrechts University of Kiel, Hermann-Rodewald-Strasse 6, Kiel 24098, Germany.
authors.forename: Anne-Christi
authors.initials: AC
authors.lastname: Graeser
authors.forename: Katri
authors.initials: K
authors.lastname: Giller
authors.forename: Heike
authors.initials: H
authors.lastname: Wiegand
authors.forename: Luca
authors.initials: L
authors.lastname: Barella
authors.forename: Christine
authors.initials: C
authors.lastname: Boesch Saadatmandi
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D002807:Chondroitin / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects; D004357:Drug Synergism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005944:Glucosamine / Q000494:pharmacology; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D016877:Oxidants / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide / Q000633:toxicity
chemical_list: D053583:Interleukin-1beta; D061965:Matrix Metalloproteinase Inhibitors; D016877:Oxidants; D012333:RNA, Messenger; D002807:Chondroitin; D020122:tert-Butylhydroperoxide; D019278:Matrix Metalloproteinase 3; D024502:alpha-Tocopherol; D012643:Selenium; D005944:Glucosamine; D001205:Ascorbic Acid