- Publikační typ
- abstrakt z konference MeSH
- Klíčová slova
- N-furoylserotonin,
- MeSH
- antagonisté histaminu H1 MeSH
- antioxidancia klasifikace MeSH
- beta blokátory MeSH
- flavonoidy farmakologie klasifikace MeSH
- kaspasa 3 účinky léků MeSH
- lidé MeSH
- luminiscence MeSH
- neutrofily * imunologie patologie účinky léků MeSH
- peroxidasa účinky léků MeSH
- polyfenoly farmakologie klasifikace MeSH
- proteinkinasa C účinky léků MeSH
- reaktivní formy kyslíku škodlivé účinky MeSH
- respirační vzplanutí * účinky léků MeSH
- superoxiddismutasa MeSH
- výzkum MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Rheumatoid arthritis (RA) is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT), with methotrexate (MTX), the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA) in male Lewis rats. The experiment included healthy controls (CO), arthritic animals (AA), AA given N-f-5HT (AA-N-f-5HT), and AA given MTX (AA-MTX). N-f-5HT did not affect the body weight change and clinical parameters until the 14th experimental day. Its positive effect was rising during the 28-day experiment, indicating a delayed onset of N-f-5HT action. Administration of either N-f-5HT or MTX caused reduction of inflammation measured as the level of CRP in plasma and the activity of LOX in the liver. mRNA transcription of TNF-α and iNOS in the liver was significantly attenuated in both MTX and N-f-5HT treated groups of arthritic rats. Interestingly, in contrast to MTX, N-f-5HT significantly lowered the level of IL-1β in plasma and IL-1β mRNA expression in the liver and spleen of arthritic rats. This speaks for future investigations of N-f-5HT as an agent in the treatment of RA in combination therapy with MTX.
- MeSH
- arachidonátlipoxygenasy genetika metabolismus MeSH
- artritida experimentální farmakoterapie genetika patologie MeSH
- biologické markery MeSH
- C-reaktivní protein MeSH
- časové faktory MeSH
- cytokiny krev genetika metabolismus MeSH
- játra účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- mediátory zánětu * MeSH
- methotrexát farmakologie MeSH
- modely nemocí na zvířatech MeSH
- orgánová specificita MeSH
- regulace genové exprese účinky léků MeSH
- serotonin analogy a deriváty farmakologie MeSH
- stupeň závažnosti nemoci MeSH
- transkriptom * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The effect of three therapeutically used drugs and five polyphenolic compounds on the mechanism of oxidative burst was compared in whole blood and isolated neutrophils at cellular and molecular level. In 10 microM concentration, the compounds investigated decreased the oxidative burst of whole blood in the rank order of potency: N-feruloylserotonin (N-f-5HT) > curcumin (CUR) > quercetin (QUER) > arbutin (ARB) > resveratrol (RES) > dithiaden (DIT) > carvedilol (CARV) > brompheniramine (BPA). The ratio between the percentage inhibition of extracellular versus intracellular chemiluminescence (CL) followed the rank order QUER > N-f-5HT > RES > CUR > DIT and is indicative of the positive effect of the compounds tested against oxidative burst of neutrophils, demonstrating suppression of reactive oxygen species extracellularly with minimal alteration of intracellular reactive oxygen species (ROS). Activation of protein kinase C was significantly decreased by DIT, CUR, QUER and N-f-5HT. CARV, DIT, QUER and ARB reduced activated neutrophil myeloperoxidase release more significantly compared with the effect on superoxide anion generation. All compounds tested increased the activity of caspase-3 in cell-free system. It is suggested that other regulatory mechanisms than protein kinase C might participate in the inhibition of neutrophil activation with the compounds tested. Different mechanisms are concerned in controlling the assembly of NADPH oxidase and the regulatory role of calcium ions is suggested. Compounds decreasing the amount of extracellular ROS generation, yet affecting but minimally intracellular ROS generation, are promising for further investigation in vivo.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- neutrofily metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- respirační vzplanutí fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIMS: The diverse physiological functions of histamine are mediated through distinct histamine receptors. In this study we investigated the role of H2R and H4R in the effects of histamine on the production of reactive oxygen species by phagocytes in whole blood. MAIN METHODS: Changes in reactive oxygen species (ROS) production by whole blood phagocytes after treatment with histamine, H4R agonists (4-methylhistamine, VUF8430), H2R agonist (dimaprit) and their combinations with H4R antagonist (JNJ10191584) and H2R antagonist (ranitidine) were determined using the chemiluminescence (CL) assay. To exclude the direct scavenging effects of the studied compounds on the CL response, the antioxidant properties of all compounds were measured using several methods (TRAP, ORAC, and luminol-HRP-H2O2 based CL). KEY FINDINGS: Histamine, 4-methylhistamine, VUF8430 and dimaprit inhibited the spontaneous and OZP-activated whole blood CL in a dose-dependent manner. On the other hand, only VUF8430 was able to inhibit PMA-activated whole blood CL. Ranitidine, but not JNJ10191584, completely reduced the effects of histamine, 4-methylhistamine and dimaprit. The direct scavenging ability of tested compounds was negligible. SIGNIFICANCE: Our results demonstrate that the inhibitory effects of histamine on ROS production in whole blood phagocytes were caused by H2R. Our results also suggest that H4R agonists in concentrations higher than 10(-6)M may also influence ROS production via binding to H2R.
- MeSH
- agonisté histaminu farmakologie MeSH
- benzimidazoly farmakologie MeSH
- dimaprit farmakologie MeSH
- fagocyty účinky léků metabolismus MeSH
- guanidiny farmakologie MeSH
- histamin fyziologie MeSH
- lidé MeSH
- methylhistaminy farmakologie MeSH
- reaktivní formy kyslíku krev MeSH
- receptory histaminu H2 metabolismus MeSH
- receptory histaminu metabolismus MeSH
- receptory spřažené s G-proteiny agonisté metabolismus MeSH
- thiomočovina analogy a deriváty farmakologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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
- 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
- Publikační typ
- abstrakt z konference MeSH
It has been demonstrated that pterostilbene inhibits reactive oxygen species production in neutrophils in vitro. However, little is known about its effects on neutrophils during inflammation in vivo. In this study, the effect of pterostilbene on neutrophil activity was investigated in experimental arthritis model. Lewis rats were injected by a single intradermal injection of heat-killed Mycobacterium butyricum in Freund's adjuvant to develop arthritis. Another group of arthritic animals received pterostilbene 30 mg/kg, daily, p.o. The number and activity of neutrophils in blood were measured on a weekly basis during the whole experiment. Moreover, the total radical trapping potential in plasma was measured at the end of the experiment. In the pterostilbene treated arthritic group, the treatment significantly lowered the number of neutrophils in blood on days 14 and 21 without significant downregulation of neutrophil oxidative burst. Pterostilbene nonsignificantly increased total radical trapping potential in arthritic animals. These results indicate that the promising effects of pterostilbene on reactive oxygen species operate by different mechanisms in vitro and in the animal model of inflammation. In conclusion, the positive effects of pterostilbene in the model of arthritis may be attributed to regulation of neutrophil number.
- MeSH
- artritida experimentální farmakoterapie patologie MeSH
- down regulace účinky léků MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- nepřímá aktivace účinky léků imunologie MeSH
- neutrofily cytologie účinky léků patologie MeSH
- peroxidy metabolismus MeSH
- počet leukocytů MeSH
- potkani inbrední LEW MeSH
- reaktivní formy kyslíku metabolismus MeSH
- stilbeny chemie farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
