NITRITES/pharmacology Dotaz Zobrazit nápovědu
H1-antihistamines are known to be important modulators of inflammatory response. However, the information about the influence of these drugs on reactive nitrogen species generation is still controversial. The main aim of the present study was to investigate the effects of selected H1-antihistamines on nitric oxide production by lipopolysaccharide-stimulated murine macrophages RAW 264.7, measured as changes in inducible nitric oxide synthase (iNOS) protein expression in cell lysates by Western blotting and nitrite formation in cell supernatants using the Griess reaction. In pharmacological non-toxic concentrations, H1-antihistamines significantly inhibited nitrite accumulation that was not caused by the scavenging ability of drugs against nitric oxide, measured amperometrically. The degree of inhibition of nitrite accumulation positively correlated with the degree of tested lipophilicity, measured by reversed-phase thin layer chromatography. Furthermore, H1-antihistamines differentially modulated the iNOS protein expression. In conclusion, as was shown in this study, the modulation of nitric oxide production could be caused by the downregulation of iNOS protein expression and/or the iNOS protein activity.
- MeSH
- buněčné extrakty MeSH
- buněčné linie MeSH
- down regulace MeSH
- dusitany metabolismus MeSH
- ethylendiaminy MeSH
- lipidy chemie MeSH
- lipopolysacharidy metabolismus MeSH
- makrofágy enzymologie patologie účinky léků MeSH
- myši MeSH
- nesedativní H1-antihistaminika farmakologie chemie MeSH
- oxid dusnatý metabolismus MeSH
- sulfanilamidy MeSH
- synthasa oxidu dusnatého, typ II metabolismus MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- 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
Organické nitráty, stejně jako digitalis, patří i dnes k nepostradatelným lékům. Jako první je u anginy pectoris použil T. L. Brunton, Tate a Murrel, který roku 1879 publikoval práci o jeho aplikaci při angině pectoris. Záhy bylo potvrzeno, že účinným hemodynamickým mechanizmem amylnitritu a nitroglycerinu je vazodilatace, a to především ve venózním řečišti. Snížením venózního návratu klesá enddiastolický tlak a objem v levé i pravé komoře a spotřeba kyslíku v myokardu. William Osler byl první, kdo navrhl užití nitroglycerinu u pacientů se srdeční insuficiencí „je-li jejich pulz tvrdý“, jak píše v prvním vydání své knihy „Principles and Practice of Medicine“ z roku 1892. O padesát let později zjistil L. Goldberg ve dvojitě slepé studii, že izosorbid dinitrát snižuje zřetelně krevní tlak u hypertoniků. Izosorbid dinitrát a izosorbid 5-mononitrát jsou nyní – stejně jako nitroglycerin – užívány s úspěchem u nemocných s namáhavou i klidovou anginou pectoris a u některých nemocných se srdeční insuficiencí. Depotní formy, zejména izosorbid 5-mononitrátu se osvědčují v chronické léčbě ischemické choroby srdeční k prevenci anginózních záchvatů, aniž by vedly k toleranci. V článku jsou shrnuty též základy chemie a farmakologie organických nitrátů a nitroprusidu sodného, i zásady jejich užití v praxi. Je třeba znovu zvážit vhodnost podání depotních nitrátů u izolované systolické hypertenze starých lidí a kriticky posoudit jejich indikaci u nemocných s chronickou srdeční slabostí, zejména s ohledem na současnou konkomitantní léčbu.
Organic nitrates still constitute, like digitalis, an indispensable remedy. Amyl nitrite, discovered by Balard was the first to be used for the therapy of angina pectoris by Sir T. Lauder Brunton in 1867. Nitroglycerin (Glyceroltrinitrate) was synthetized by Ascanio Sobrero 1846 and was studied by Brunton, Tate, and Murrel who published his paper on the treatment of angina pectoris in 1879. It has been soon recognised that the main effect of nitrates is vasodilatation more pronounced in the veins, resulting in reduced venous return, decrease of left and right ventricular end-diastolic pressure and volume and in a reduction in the myocardioal oxygen demand. Sir William Osler was the first who suggested the use of nitroglycerin in patients with congestive heart failure „when the pulse is hard and firm“, in his „Principles and Practice of Medicine“ 1892. About fifty years later, L.Goldberg confirmed the antihypertensive effect of isosorbide dinitrate in a double – leticin trial on hypertensive patients. The longacting nitrates isosorbide dinitrate and isosorbide 5-mononitrate now share all the beneficial effects of nitroglycerin in patients with stable and unstable angina and in selected patients with heart failure. The sustained-release tablets of isosorbide 5-mononitrate have been shown to be effective with long-term use without inducing tolerance. The author also summaries basic data concerning the chemistry, pharmacology and clinical applications of organic nitrates and nitrocompounds. The position of nitrates in the treatment of isolated systolic hypertension in the elderly and of chronic heart failure is still to be established.
