Inhibitory and enhancing effects of piroxicam on whole blood chemiluminescence

Abstract

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.

Increased Motility and Invasiveness in Tumor Cells That Survive 10 Gy Irradiation

“…Tumor cell invasiveness is associated with the formation of focal contacts and alteration of the expression or localization of focal adhesion proteins (Alexandrova et al, 2007), including paxillin and FAK, the phosphorylations of which are critically involved in regulation of cell migration (Petit et al, 2000;Tsubouchi et al, 2002). Therefore, both facilitated cell migration and increased adhesion in IR cells can be accounted for by enhanced translocation of these molecules to focal adhesions (Fig.…”

Phytochemical analysis and gastroprotective effect of Stellaria media (L.) Vill. methanolic extract on piroxicam-induced gastric ulcer in Wistar rats

“…The SME treatment markedly restored the RBC count and Hb concentration to the normal level, which suggests that SME has the potential to protect against PRX-induced hematotoxicity by restoring RBCs and enhancing Hb concentration. In the PRXalone treated group, WBCs and PLTs increased signi cantly more than in normal control group, indicating compromised host immunity (Alexandrova et al 2007). Treatment with SME restored the WBC to normal, and it may be attributed to the markedly enhanced host's immune defense system.…”