title: On the molecular pharmacology of resveratrol on oxidative burst inhibition in professional phagocytes.
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/β II. 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.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dúbravská 9, 841 04 Bratislava, Slovakia.
authors.forename: Radomír
authors.initials: R
authors.lastname: Nosáľ
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dúbravská 9, 841 04 Bratislava, Slovakia.
authors.forename: Katarína
authors.initials: K
authors.lastname: Drábiková
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dúbravská 9, 841 04 Bratislava, Slovakia.
authors.forename: Viera
authors.initials: V
authors.lastname: Jančinová
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dúbravská 9, 841 04 Bratislava, Slovakia.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Perečko
authors.affiliation: Institute of Biophysics AS CR v.v.i. Královopolská 135, 612 65 Brno, Czech Republic.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Ambrožová
authors.affiliation: Institute of Biophysics AS CR v.v.i. Královopolská 135, 612 65 Brno, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Číž
authors.affiliation: Institute of Biophysics AS CR v.v.i. Královopolská 135, 612 65 Brno, Czech Republic.
authors.forename: Antonín
authors.initials: A
authors.lastname: Lojek
authors.affiliation: Institute of Biophysics AS CR v.v.i. Královopolská 135, 612 65 Brno, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Pekarová
authors.affiliation: Institute of Chemical Technology, Faculty of Food and Biochemical Technology, Technická 5, 166 28 Praha 6, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Šmidrkal
authors.affiliation: Institute of Organic Chemistry and Biochemistry AS CR v.v.i., Flemmingovo nám. 2, 166 10 Praha 6, Czech Republic.
authors.forename: Juraj
authors.initials: J
authors.lastname: Harmatha
mesh_terms: D000818:Animals; D002460:Cell Line; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008163:Luminescent Measurements; D008165:Luminol / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D009573:Nitrites; D017382:Reactive Oxygen Species; D013267:Stilbenes; D017392:Thiobarbituric Acid Reactive Substances; D008165:Luminol; D052247:Nitric Oxide Synthase Type II; D011494:Protein Kinases; D013755:Tetradecanoylphorbol Acetate; D000077185:Resveratrol