NO causes depolarization of the mitochondria in normal chondrocytes The relative ratio of red green fluorescence Ceritinib CAS intensity values showed that in normal human chondrocyte cultures 1 mM SNP at 24 hours decreased the Inhibitors,Modulators,Libraries ratio of red green fluorescence in compar ison with untreated cells. In addition, 1 mM SNP caused an increase in the cell population with mitochondrial depo larization. On the other hand, NOC 12 induced mito chondrial depolarization, as the percentage of cells with normal polarization diminished, with 1 mM NOC 12 at 24 hours, Inhibitors,Modulators,Libraries 27. 7 17. 9 versus 14. 1 3. 6, P 0. 05, and the percentage of cells with depolarization increased, 12. 2 6. 6 versus 18. 8 11. 3, P 0. 05. This finding also can be observed with decreasing ratio of red green fluorescence in comparison with untreated cells.

However, the NO donor that induced the strongest changes in Inhibitors,Modulators,Libraries the mitochondrial membrane potential was SNP. NO abolishes ATP generation by chondrocytes in culture NO has a detrimental effect on the generation of ATP by normal chondrocytes. With NOC 12, the intracellular ATP levels were significantly lower than in control cells, with 1mM NOC 12 at 24 hours, 0. 40 0. 16 versus 0. 57 0. 19. Again, the NO donor that induced the most dramatic changes was SNP, as it reduced the intracellular ATP levels practi cally to zero. Chondrocytic lactate production is strongly influenced by NO donor type NO donors have very different effects on lactate release by normal articular chondrocytes. The only donor that induced a significant fall in these values was SNP, with 2 mM SNP at 24 hours, 1. 01 0.

3 versus 2. 30 0. 58. The new generation donor NOC 12 induced a substantial increase in lactate production, Inhibitors,Modulators,Libraries with 0. 5 mM NOC 12 at 24 hours, 2. 91 0. 58 versus 2. 30 0. 58, although this increase was not statistically significant. SNP reduces glucose uptake by normal articular chondrocytes Uptake of 2 DG by normal Inhibitors,Modulators,Libraries chondrocytes cultured under uM SNP concentrations for either 15 minutes or 1 hour was approximately 20% lower than that found in their respective controls. On the contrary, 2 DG uptake in normal chondro cytes stimulated with NOC 12 did not change relative to the control. In this set of experiments, uM NO donors concentrations were employed, the reason is because in most of these cases, when mM concentra tions were used, this caused the cells to rise and the quantifications showed false positives.

Detrimental effect of NO on chondrocyte viability depends on glucose levels To assess the impact of glucose levels on cell viability after NO treatment, we carried out experiments with both NO donors using only one constant concentration and increasing glucose concentrations. The percentage of death cells decreased as glucose concentration increased, add to favorites only when SNP was employed as NO donor. No significant results were found in this issue when NOC 12 was used.