Inhibitory and enhancing effects of piroxicam on whole blood chemiluminescence.
The effects of piroxicam on the production of reactive oxygen species by stimulated phagocytes was studied in whole blood by a chemiluminescence (CL) technique in relation to maximum activity, localization and kinetics of radical generation. We found that piroxicam dose-dependently inhibited total (intra- and extracellular) zymosan-stimulated luminol CL (LCL) at a high stimulant concentration (p = 0.0001). Piroxicam additionally decreased cytochalasin B-reduced LCL, which shows that the effect of the drug should be sought in the extracellular component of the response. Piroxicam inhibited the first phase of extracellular LCL in a dose-dependent manner (p = 0.0001) and revealed itself as an enhancing agent of CL in later time intervals after the start of respiratory burst, in a model system containing horseradish peroxidase (HRP) and sodium azide. It enhanced LCL of a cell-free system, i.e. influenced the CL due to HRP-catalysed decomposition of hydrogen peroxide. It also dose-dependently inhibited the early extracellular superoxide production, evaluated by lucigenin CL (p = 0.022). Piroxicam inhibited the total fMLP-stimulated LCL by 70% approximately and, only by about 30%, the first phase of fMLP-stimulated extracellular LCL, which presupposes an effect on myeloperoxidase-catalysed formation of hypochloric acid. Piroxicam slightly increased the intracellular LCL by phagocytes (p = 0.02), an effect that is probably connected with its ability to induce the release of secondary messengers in signal transduction. In conclusion, the anti-inflammatory effect of piroxicam is probably related to the inhibition of the extracellular generation of superoxide and hypochloric acid in the early stages of phagocyte activation.
Alexandrova
Margarita L
ML
Department of Biophysics, Medical University, Pleven, Bulgaria. margalexandrova@hotmail.com
Bochev
Petyo G
PG
Markova
Vanya I
VI
D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D049449:Luminescence; D008163:Luminescent Measurements; D010586:Phagocytes / Q000737:chemistry / Q000187:drug effects*; D010894:Piroxicam / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000032:analysis*; D015054:Zymosan / Q000494:pharmacology
D017382:Reactive Oxygen Species; D010894:Piroxicam; D003571:Cytochalasin B; D015054:Zymosan