Tatiana Mačičková

Quercetin inhibits degranulation and superoxide generation in PMA stimulated neutrophils

Abstract Activated neutrophils represent the main source of myeloperoxidase (MPO), superoxide (SO) and subsequently derived oxygen metabolites. They have important microbicidal activities, however in inflammatory conditions they may secondarily attack surrounding tissues. Overproduction of reactive oxygen species, prolonged or excessive liberation of MPO and other effective yet also toxic substances from neutrophils may participate in disturbed apoptosis, intensify the inflammatory processes and result in serious human diseases. The inhibitory effect of quercetin on PMA stimulated SO generation in isolated human neutrophils was found to be dosedependent, without affecting the activity of intact isolated neutrophils. At comparable conditions, quercetin was more potent in inhibiting MPO release than SO generation. Our results indicate that quercetin could support resolution of inflammation through decreased activity of neutrophils, i.e. respiratory burst and degranulation.

Arbutin and decrease of potentially toxic substances generated in human blood neutrophils.

ABSTRACT Neutrophils, highly motile phagocytic cells, constitute the first line of host defense and simultaneously they are considered to be central cells of chronic inflammation. In combination with standard therapeutic procedures, natural substances are gaining interest as an option for enhancing the effectiveness of treatment of inflammatory diseases. We investigated the effect of arbutin and carvedilol and of their combination on 4β-phorbol-12β-myristate-13α-acetate- stimulated functions of human isolated neutrophils. Cells were preincubated with the drugs tested and subsequently stimulated. Superoxide (with or without blood platelets, in the rate close to physiological conditions [1:50]) and HOCl generation, elastase and myeloperoxidase release were determined spectrophotometrically and phospholipase D activation spectrofluorometrically. The combined effect of arbutin and carvedilol was found to be more effective than the effect of each compound alone. Our study provided evidence supporting the potential beneficial effect of arbutin alone or in combination with carvedilol in diminishing tissue damage by decreasing phospholipase D, myeloperoxidase and elastase activity and by attenuating the generation of superoxide and the subsequently derived reactive oxygen species. The presented data indicate the ability of arbutin to suppress the onset and progression of inflammation

Protective effect of pheniramines against mesenteric ischaemia/reperfusion-induced injury

Mesenteric ischaemia/reperfusion (I/R) leading to inflammation is accompanied by activation of neutrophils. Pheniramines, a group of H1 antihistamines, decrease free radical formation by activated neutrophils in vitro in this order: pheniramine< chlorpheniramine< brompheniramine [1]. Halogen substitution in the pheniramine molecule increases lipophilicity; compared to pheniramine, chlorand brompheniramine possess greater lipophilicity. Enhanced binding of pheniramines to membranes may therefore inhibit radical formation and/ or liberation [2]. This antioxidative activity of H1 antihistamines is considered beneficial as it could decrease tissue damage. Aims of this study were to (1) examine evidence for intestinal damage and free radical formation in an in vivo model of I/R induced by occlusion of the superior mesentery artery (SMA); (2) investigate influence of halogenation on protective and antiradical activity of pheniramines in vivo.

Effect of stilbene derivative on superoxide generation and enzyme release from human neutrophils in vitro

Abstract Neutrophils represent the body´s primary line of defense against invading pathogens. They most rapidly reach the site of injury or infection, liberate antimicrobial proteins, proteases and produce reactive oxygen species. Prolonged or excessive liberation of these very effective and toxic substances could intensify the inflammatory process and enhance tissue damage in many diseases, such as allergies, infections and rheumatoid arthritis. Pterostilbene belongs to stilbenoids, structural analogues of resveratrol, which act as natural protective agents in defending the plant against viral and microbial attack. It possesses anticancerous, antidiabetic and anti-inflammatory properties. The study provides new information on the effect of pterostilbene [0.01-100 μmol/l] on superoxide generation in and myeloperoxidase (MPO) release from azurophil granules of isolated human neutrophils. PMA [1 μmol/l], which activates NADPH-oxidase via protein kinase C, was used for stimulation of neutrophils Unstimulated cells showed neither superoxide generation nor myelopereoxidase release after preincubation with the drug studied. Pterostilbene dose dependently decreased superoxide generation in and MPO release from stimulated human neutrophils, however a significant decrease was recorded only in the concentration 100 μmol/l. The effect of pterostilbene was more pronounced on superoxide generation in comparison to MPO release. Our results suggest that the effect of pterostilbene may prove beneficial in controlling inflammation.

Further studies on the mechanism of antiphagocyte-antioxidative effect of H1-antihistamines

-receptor antago-nists possess other pharmacological properties; anti-infl am-matory action, inhibition of blood platelet function and antioxidative effects [1, 2]. The mechanism(s) responsible for the nonspecifi nett comparison test after parametric analysis of variance (ANOVA) for c non-receptor operated activity of H

Extra- and intracellular oxidant production in phorbol myristate acetate stimulated human polymorphonuclear leukocytes: modulation by histamine and H1-antagonist loratadine

No Abstract..

Pharmacological intervention with oxidative burst in human neutrophils

Abstract In this study we investigated the effect of five therapeutically used drugs and four natural polyphenolic compounds on the mechanism of oxidative burst of human neutrophils concerning their participation in the generation of reactive oxygen species (ROS). The compounds investigated decreased the oxidative burst of whole blood in the rank order of potency: N-feruloylserotonin > quercetin > curcumin > arbutin > dithiaden > carvedilol. The generation of intracellular reactive oxygen species in isolated neutrophils decreased in the same rank order, while carvedilol was ineffective. Scavenging of extracellular oxygen radicals followed the rank order of potency: N-feruloylserotonin > curcumin > quercetin > dithiaden. Arbutin and carvedilol had no effect. All compounds tested increased the activity of caspase-3 in cell-free system indicating a positive effect on apoptosis of neutrophils. Activation of protein kinase C was significantly decreased by dithiaden, curcumin, quercetin and N-feruloylserotonin. Carvedilol, dithiaden, quercetin and arbutin reduced activated neutrophil myeloperoxidase release more significantly compared with their less pronounced effect on superoxide generation The presented results are indicative of pharmacological intervention with neutrophils in pathological processes. Of particular interest was the effect of natural compounds. Intracellular inhibition of oxidative burst in isolated neutrophils by the drugs tested and natural antioxidants has to be further analysed since ROS play an important role in immunological responses of neutrophils.