Budesonide Reduces Superoxide and Peroxynitrite Anion Chemiluminescence during Human Neutrophil Bursts

Abstract

Many lung disorders are characterized by airway inflammation involving the recruitment of inflammatory cells, and leading to the release of oxidant and inflammatory mediators. The overproduction of superoxide anion (O₂^–DELETE) and nitric oxide (NO) during the respiratory bursts of neutrophils leads to production of peroxynitrite, a highly damaging oxidant with an important role in the inflammatory loop causing airway hyper-reactivity in respiratory diseases like asthma. The aim of this study was to investigate in vitro the effects of a 1-hour incubation with budesonide at 2.5 × 10^–7, 5 × 10^–7, 1 × 10^–6, 2 × 10^–6 and 4 × 10^–6 mol/l on O₂^–DELETE, NO, and peroxynitrite production during the respiratory burst of human neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP, 5 × 10^–7 mol/l) or phorbol 12-myristate 13-acetate (PMA, 2 × 10^–6 mol/l), as documented by luminol-amplified chemiluminescence (LACL). In absence of L-arginine, budesonide (5 × 10^–7 to 4 × 10^–6 mol/l) dose-dependently reduced both fMLP- and PMA-induced LACL (18.3–50.6%). In the presence of L-arginine (100 µg/ml), a NO donor increasing peroxynitrite production, LACL increased 3–5 times compared with baseline, but budesonide dose-dependently reduced LACL (25.5–59.6%). Mifepristone (4 × 10^–6 mol/l), a glucocorticoid receptor antagonist, inhibited the effect of budesonide on LACL, thus confirming that budesonide reacts with glucocorticoid receptors to exert an antioxidant activity. These results suggest that budesonide target rapidly human neutrophils leading to a fast reduction in both NO and peroxynitrite production, and are consistent with decrease in exhaled NO levels after treatment with budesonide in patients with asthma.

Effect of formoterol and budesonide on chemokine release, chemokine receptor expression and chemotaxis in human neutrophils

“…respiratory burst) (127). As CXCL1 had a down-regulating effect only when combined with formoterol and/or budesonide, it is interesting that both salmeterol and budesonide have been shown to reduce the respiratory burst in neutrophils (128,129).…”

Effects of intratracheal budesonide during early postnatal life on lung maturity of premature fetal rabbits

“…30 Some other studies also showed that the high lipophilicity of BUD, the high solubility of BUD in PS, and its high affinity with the lung tissue made BUD a better choice in terms of the anti-inflammatory, anti-oxidative, and pulmonary edema-reducing effects of glucocorticoids. [31][32][33] It should be noted that, for intratracheal administration of BUD using exogenous surfactant as a carrier, the effect of BUD on the surface activity of surfactant depend on the selection of the surfactant preparation, as well as their mixing ratio. 34,35 If Infasurf, a cholesterolcontaining surfactant preparation, is used to deliver BUD at a concentration higher than 1%, BUD may significantly compromise its surface activity.…”

A Combination of Budesonide and the SH-Metabolite I of Erdosteine Acts Synergistically in Reducing Chemiluminescence during Human Neutrophil Respiratory Burst

“…BUD and erdosteine (through Met I) are both active in reducing the release of O 2 -ؒ , NO and ONOO - [23,30,31] , and are usually administered in patients with respiratory diseases. PMNs are major sources of ROS and peroxynitrite production, but the effects of combining Met I and BUD have not yet been analyzed at this level.…”