Nejvíce citovaný článek - PubMed ID 17465695
The influence of wine polyphenols on reactive oxygen and nitrogen species production by murine macrophages RAW 264.7
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.
- MeSH
- buněčné linie MeSH
- dusitany metabolismus MeSH
- fagocyty účinky léků enzymologie metabolismus MeSH
- látky reagující s kyselinou thiobarbiturovou metabolismus MeSH
- lidé MeSH
- luminiscenční měření MeSH
- luminol metabolismus MeSH
- myši MeSH
- neutrofily účinky léků metabolismus MeSH
- peroxidace lipidů účinky léků MeSH
- proteinkinasy metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- respirační vzplanutí účinky léků MeSH
- resveratrol MeSH
- scavengery volných radikálů metabolismus MeSH
- separace buněk MeSH
- stilbeny farmakologie MeSH
- synthasa oxidu dusnatého, typ II metabolismus MeSH
- tetradekanoylforbolacetát farmakologie MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dusitany MeSH
- látky reagující s kyselinou thiobarbiturovou MeSH
- luminol MeSH
- proteinkinasy MeSH
- reaktivní formy kyslíku MeSH
- resveratrol MeSH
- scavengery volných radikálů MeSH
- stilbeny MeSH
- synthasa oxidu dusnatého, typ II MeSH
- tetradekanoylforbolacetát MeSH
Neutrophils represent the front-line defence cells in protecting organisms against infection and play an irreplaceable role in the proper performance of the immune system. As early as within the first minutes of stimulation, neutrophilic NADPH oxidase is activated, and cells release large quantities of highly toxic reactive oxygen species (ROS). These oxidants can be highly toxic not only for infectious agents but also for neighboring host tissues. Since flavonoids exhibit antioxidant and anti-inflammatory effects, they are subjects of interest for pharmacological modulation of ROS production. The present paper summarizes contemporary knowledge on the effects of various flavonoids on the respiratory burst of mammalian neutrophils. It can be summarized that the inhibitory effects of flavonoids on the respiratory burst of phagocytes are mediated via inhibition of enzymes involved in cell signaling as well as via modulation of redox status. However, the effects of flavonoids are even more complex, and several sites of action, depending upon the flavonoid structure and way of application, are included.
- MeSH
- flavonoidy farmakologie MeSH
- neutrofily cytologie účinky léků metabolismus MeSH
- polyfenoly farmakologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- respirační vzplanutí účinky léků MeSH
- savci metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- flavonoidy MeSH
- polyfenoly MeSH
- reaktivní formy kyslíku MeSH
BACKGROUND: Polyunsaturated fatty acids (PUFAs) can affect various functions of the immune system including inflammatory responses. An oxidative burst of phagocytes accompanied by reactive oxygen species (ROS) and reactive nitrogen species (RNS) formation is one of the phagocyte functions that could be modulated by PUFAs. AIM OF THE STUDY: To investigate the effects of omega-3 (alpha-linolenic, docosahexaenoic, eicosapentaenoic) and omega-6 (arachidonic, linoleic) PUFAs on lipopolysaccharide (LPS)-stimulated ROS and RNS production by the murine macrophage cell line RAW 264.7. METHODS: Murine peritoneal macrophages RAW 264.7 were stimulated with LPS (0.1 microg/ml) and treated with 0.1-100 microM omega-3 or omega-6 PUFAs for either 8 (ROS production) or 20 h (RNS production). The cytotoxicity of PUFAs was evaluated by an ATP (adenosine triphosphate) test after both 8 and 20 h of treatment with PUFAs. Changes in ROS production by LPS-treated macrophages subsequently activated with phorbol myristate acetate (PMA) or opsonized zymosan particles (OZP) were determined by luminol-enhanced chemiluminescence, whilst the production of RNS was determined as the concentration of nitrites in cell supernatants (Griess reaction). Changes in inducible nitric oxide synthase (iNOS) expression were evaluated by Western blot analysis. The antioxidant properties of PUFAs were tested by TRAP (total peroxyl radical-trapping antioxidant parameter) assay. RESULTS: All PUFAs in 100 microM concentration except eicosapentaenoic acid decreased ROS production. The effect was most significant when docosahexaenoic acid was used. Arachidonic acid decreased PMA-activated ROS production even in 1 and 10 microM concentrations. On the other hand, 10 and 100 microM eicosapentaenoic acid potentiated ROS production. As concerns RNS production, all the fatty acids that were tested in a concentration of 100 microM decreased iNOS expression and nitrite accumulation. Fatty acids had no significant effect on the viability and proliferation of RAW 264.7 cells. The TRAP assay confirmed that none of the tested PUFAs exerted any significant antioxidant properties. CONCLUSION: High concentrations of PUFAs of both omega-3 and omega-6 groups can inhibit ROS and RNS formation by stimulated macrophages. The expression of iNOS can also be inhibited. This effect, together with the absence of antioxidant activity and cytotoxic properties, indicates that PUFAs can participate in the regulation of enzymes responsible for reactive species production.
- MeSH
- časové faktory MeSH
- dusík metabolismus MeSH
- dusitany metabolismus MeSH
- elektroforéza v polyakrylamidovém gelu MeSH
- kultivované buňky MeSH
- luminiscenční měření metody MeSH
- makrofágy účinky léků metabolismus MeSH
- myši MeSH
- nenasycené mastné kyseliny farmakologie MeSH
- oxidační stres účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- synthasa oxidu dusnatého účinky léků metabolismus MeSH
- viabilita buněk účinky léků MeSH
- western blotting metody MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dusík MeSH
- dusitany MeSH
- nenasycené mastné kyseliny MeSH
- reaktivní formy kyslíku MeSH
- synthasa oxidu dusnatého MeSH
The effect is described of selenium supplemented in an inorganic and organic form on the innate immune response of goats. Though the phagocytic activity (as a marker of the immune function) was found to be lower in organic-Se-treated group than in control (54.5 +/- 4.32 vs. 60.2 +/- 9.15 %), it did not generally exhibit any significant differences; similarly, no differences were found in the phagocytic index. The production of reactive oxygen species (ROS) was determined using the luminol-enhanced chemiluminescence (CL) (estimated as peak CL, integral CL and a peak time after addition of calcium ionophore A23187, opsonised zymosan (OZP) and phorbol-12-myristate-13-acetate as effectors. A significant ROS increase reflected in integral CL and a peak time was found in the inorganic-Se-treated group when OZP was used as activator; other parameters did not exhibit significant changes. The supplementation of Se in inorganic form can thus be seen to influence positively the innate immune system of kids.
- MeSH
- anorganické látky aplikace a dávkování MeSH
- fagocytóza účinky léků MeSH
- imunologické faktory aplikace a dávkování MeSH
- kozy MeSH
- organické látky aplikace a dávkování MeSH
- přirozená imunita účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- selen aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- anorganické látky MeSH
- imunologické faktory MeSH
- organické látky MeSH
- reaktivní formy kyslíku MeSH
- selen MeSH