On the Molecular Pharmacology of Resveratrol on Oxidative Burst Inhibition in Professional Phagocytes

Radomír Nosáľ,Milan Číž,Katarína Drábiková,Michaela Pekarová,Viera Jančinová,Tomáš Perečko,Gabriela Ambrožová,Jan Šmidrkal,Antonín Lojek,Juraj Harmatha

doi:10.1155/2014/706269

Abstract

Resveratrol—3,5,4′-trihydroxystilbene—possesses antioxidant activities in vitro. It dose-dependently inhibited the generation of peroxyl, hydroxyl, peroxides, and lipid peroxidation products in cell free systems. Oxidative burst of whole human blood stimulated with PMA, fMLP, OpZ, and A23187 was inhibited in a concentration-dependent way, indicating suppression of both receptor and nonreceptor activated chemiluminescence by resveratrol. Results from isolated human neutrophils revealed that resveratrol was active extracellularly as well as intracellularly in inhibiting the generation of reactive oxygen species. Liberation of ATP and analysis of apoptosis showed that in the concentration of 100 μM, resveratrol did not change the viability and integrity of isolated neutrophils. Western blot analysis documented that resveratrol in concentrations of 10 and 100 μM significantly decreased PMA-induced phosphorylation of PKC α/βII. Dose-dependent inhibition of nitrite production and iNOS protein expression in RAW 264.7 cells indicated possible interference of resveratrol with reactive nitrogen radical generation in professional phagocytes. The results suggest that resveratrol represents an effective naturally occurring substance with potent pharmacological effect on oxidative burst of human neutrophils and nitric oxide production by macrophages. It should be further investigated for its pharmacological activity against oxidative stress in ischaemia reperfusion, inflammation, and other pathological conditions, particularly neoplasia.

Highlights

Neutrophils are present in high numbers in areas of inflammation, where they constitute an important source of reactive oxygen species (ROS)
We investigated the effect of RES on the mechanism of oxidative burst in human whole blood, isolated neutrophils at extra- and intracellular level, activation of protein kinase C, caspase-3 activity and cellular viability and on free radical scavenging activity in cell free systems
There was no significant difference between the stimuli applied and chemiluminescence decrease of whole blood indicating that RES may not act only as an extracellular scavenger but suppresses oxidative burst intracellularly

Summary

Introduction

Neutrophils are present in high numbers in areas of inflammation, where they constitute an important source of reactive oxygen species (ROS). Neutrophils are implicated in tissue-damaging inflammatory reactions that underlie the pathogenesis and exacerbation of many inflammatory diseases [1, 2]. Apoptosis is critical for the regulation of life span of circulating as well as emigrated neutrophils. Accumulating evidence indicates that neutrophil apoptosis is one of the critical determinants of the outcome of the inflammatory response and is a potential target for therapeutic interventions. The apoptotic neutrophil and the process of cell death exert anti-inflammatory effects that have been shown to be of therapeutic value in inflammatory diseases [5, 6]

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Results

Conclusion