In vitro Effect of Carvedilol on Professional Phagocytes

Abstract

Aim: Superfluous reactive nitrogen and oxygen species generation is implicated in the damage of tissues at sites of inflammation where activated neutrophils and macrophages are involved. This study was conducted to investigate whether the beneficial effects of carvedilol involve modulation of respiratory burst, degranulation-myeloperoxidase release and inducible nitric oxide synthase (iNOS) expression. Methods: Spectrophotometry and chemiluminescence were used to evaluate the effect of carvedilol on opsonized zymosan (0.5 mg/ml)- or N-formyl-methionyl-leucyl-phenyl-alanine (fMLP, 0.1 µmol/l)-stimulated superoxide generation and myeloperoxidase release in human neutrophils. Western blot analysis was used for iNOS expression and Griess reagent for nitric oxide production in RAW 264.7 macrophages (lipopolysaccharide (0.1 µg/ml) stimulated). Results: Carvedilol (10 and 100 µmol/l) significantly decreased opsonized zymosan- and fMPL-stimulated superoxide generation and myeloperoxidase release. Carvedilol (100 µmol/l) enhanced the effect of wortmannin (50 nmol/l), a specific inhibitor of 1-phosphatidylinositol 3-kinase and decreased iNOS expression and nitric oxide production. Conclusion: Carvedilol appears to have a non-specific effect on membranes and to interfere with the phospholipase D signaling pathway, with subsequent inhibition of reactive oxygen species generation and myeloperoxidase release, without affecting iNOS expression.

Modulation of Cytokine Secretion and Oxidative Metabolism of Innate Immune Effectors by Rhodococcus Biosurfactant

“…Luminol (10 -5 M) served as a marker LDCL. Luminescence of this agent is nonselective to oxygen-containing radicals [13]. The results were recorded on a Guardian liquid scintillation counter (Wallac) for 1 h.…”

Nitric Oxide and its Role in Cardiovascular Diseases

“…In addittion, one in vivo study using rats indicated that the drug decreased arterial pressure whilst it increased NO production [82]. On the other side, Pecivova et al reported that carvedilol does not affect the expression of iNOS by macrophages [83] and Yoshioka et al, (2000) demonstrated a novel effect of carvedilol as a NO quenching agent. Their results indicate that carvedilol directly interacts with NO in a cell-free system [84].…”

On the Pharmacology of Oxidative Burst of Human Neutrophils

“…The development of pharmacological procedures to ameliorate undesirable ROS production may become one of the central issues in research on aging and oxidative stress-related diseases in the near future. A number of therapeutically used medicaments and natural products acted not only as extracellular scavengers but they also suppressed intracellular formation of ROS in human neutrophils (Drábiková et al 2006, 2013, Jančinová et al 2012a,b, 2015, Nosáľ et al 2006, Pečivová et al 2007. Since the optimum therapy is expected to minimize tissue damage without reduction of neutrophil physiological function, separate analysis of extra-and intracellular effects of antioxidants is of particular importance (El-Benna et al 2010).…”