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: | Christine Boesch Saadatmandi, Katri Giller, Luca Barella, Anne-Christi Graeser, Gerald Rimbach, Heike Wiegand |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Antioxidant
medicine.medical_treatment Interleukin-1beta alpha-Tocopherol Pharmaceutical Science medicine.disease_cause Analytical Chemistry chemistry.chemical_compound tert-Butylhydroperoxide Glucosamine Drug Discovery Cells Cultured chemistry.chemical_classification Tocopherol Cell Death Drug Synergism Oxidants Metalloproteinases Biochemistry Chemistry (miscellaneous) Molecular Medicine Ascorbic acid Matrix Metalloproteinase 3 Chondroitin Cell Survival Glucosamine Sulfate Matrix Metalloproteinase Inhibitors Gene Expression Regulation Enzymologic Article lcsh:QD241-441 Selenium Chondrocytes lcsh:Organic chemistry Cell Line Tumor medicine Humans RNA Messenger Chondroitin sulfate Physical and Theoretical Chemistry Inflammation Reactive oxygen species Organic Chemistry Molecular biology chemistry Cytoprotection Oxidative stress |
| Zdroj: | Molecules Volume 15 Issue 1 Pages: 27-39 Molecules, 15 (1) Molecules, Vol 15, Iss 1, Pp 27-39 (2009) |
| ISSN: | 1420-3049 |
| DOI: | 10.3929/ethz-b-000081989 |
| 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. Molecules, 15 (1) ISSN:1420-3049 |
| Databáze: | OpenAIRE |
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