Juraj Harmatha, Zdeněk Zídek, Eva Kmoníčkova and Jan Šmidrkal
Immunobiological properties of selected natural and chemically modified phenylpropanoids
Effects of natural and structurally transformed lignans compared with stilbenes or stilbenoids on production of nitric oxide (NO) triggered by lipopolysaccharide (LPS) and interferon-γ (IFN-γ), tested under in vitro conditions using murine resident peritoneal macrophages, are reviewed. Relation between the molecular structure and immunobiological activity was investigated, and implication of substituents, double bond stereochemistry, or cyclic attachments (double bond geometry fixation) was assessed. The focus was on lignans and stilbenoids because they were originally selected for a joint project of common interest to phytochemical and pharmacological investigation and because they represent well interesting and universally attractive groups of polyphenols with a feasible potential for therapeutic or nutraceutic utilization.
Tomáš Perečko, Katarína Drábiková, Radomír Nosáľ, Juraj Harmatha and Viera Jančinová
Chronic inflammatory diseases, e.g. rheumatoid arthritis or cystic fibrosis, are characterised by neutrophil infiltration in inflamed tissues. Dysregulated neutrophil death may contribute to the pathogenesis of diseases where neutrophils play a role. Stilbene derivatives are reported to activate apoptosis in different cell lines. Neutrophils from healthy volunteers were incubated in vitro with resveratrol, pterostilbene, pinosylvin or piceatannol (1-100 μmol/l), and cytotoxicity and apoptosis were measured by luminometry and flow cytometry, respectively. Enhancement and/or inhibition of human recombinant caspase-3 enzyme activity were measured by luminometry. None of the stilbene derivatives tested increased ATP liberation from human neutrophils, thus showing no direct cytotoxicity effect. Resveratrol and piceatannol (100 μmol/l) treated neutrophils had a higher rate of apoptosis compared to non-treated cells. Pterostilbene and pinosylvin (1 μmol/l), yet not resveratrol or piceatannol, increased the activity of caspase-3. However in the concentration of 100 μmol/l, all stilbene derivatives tested inhibited caspase-3 activity. Their effects on human neutrophil apoptosis differed according to the structure of the molecule. Additional studies are required to get insight into the mechanisms involved in the effects of the substances tested on neutrophil viability.
Juraj Racko, Miroslav Mikolášek, Peter Benko, Ondrej Gallo, Ladislav Harmatha, Ralf Granzner and Frank Schwierz
Coupled Defect Level Recombination in the P—N Junction
The well known Shockley-Read-Hall (SRH) model considers emission and capture processes at defects exhibiting a single level or multiple non-coupled levels in the band gap of the semiconductor. The present paper generalizes the model to the case of two mutually coupled defect levels acting as trapping centres. If the intercenter transition is not considered, the model reduces to the case of two non-coupled levels treated by the SRH model.
Katarína Drábiková, Tomáš Perečko, Radomír Nosáľ, Juraj Harmatha, Jan Šmidrkal and Viera Jančinová
The study provides new information on the effect of natural polyphenols (derivatives of stilbene - resveratrol, pterostilbene, pinosylvin and piceatannol and derivatives of ferulic acid - curcumin, N-feruloylserotonin) on the activity of human neutrophils in influencing oxidative burst. All the polyphenols tested were found to reduce markedly the production of reactive oxygen species released by human neutrophils on extra-and intracellular levels as well as in cell free system. Moreover, pinosylvin, curcumin, N-feruloylserotonin and resveratrol decreased protein kinase C activity involved in neutrophil signalling and reactive oxygen species production. Our results suggest that due to their anti-neutrophil activity, the polyphenols tested might be attractive candidates in therapeutic development.
Tatiana Mačičková, Jana Pečivová, Juraj Harmatha, Klára Sviteková and Radomír Nosáľ
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.
Viera Jančinová, Tomáš Perečko, Juraj Harmatha, Radomír Nosáľ and Katarína Drábiková
Prolonged or excessive formation and liberation of cytotoxic substances from neutrophils intensifies inflammation and the risk of tissue damage. From this perspective, administration of substances which are able to reduce activity of neutrophils and to enhance apoptosis of these cells may improve the therapy of pathological states connected with persistent inflammation. In this short review, neutrophil oxidative burst and apoptosis are presented as potential targets for pharmacological intervention. Effects of natural polyphenols (resveratrol, pterostilbene, pinosylvin, piceatannol, curcumin, N-feruloylserotonin) are summarised, considering the ability of these compounds to affect inflammation and particularly neutrophil activity. The intended neutrophil inhibition is introduced as a part of a new strategy for pharmacological modulation of chronic inflammatory processes, focused on supporting innate antiinflammatory mechanisms and enhancing resolution of inflammation.
Frantisek Drafi, Katarina Bauerova, Viera Kuncirova, Silvester Ponist, Danica Mihalova, Tatiana Fedorova, Juraj Harmatha and Radomir Nosal
Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. A certain correlation was observed between oxidative stress, arthritis and the immune system. Reactive oxygen species produced in the course of cellular oxidative phosphorylation and by activated phagocytic cells during oxidative burst, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein, lipids, nucleic acids, and matrix components. Patients with rheumatoid arthritis have an altered antioxidant defense capacity barrier. In the present study the effect of substances with antioxidative properties, i.e. pinosylvin and carnosine, was determined in monotherapy for the treatment of adjuvant arthritis (AA). Moreover carnosine was evaluated in combination therapy with methotrexate. Rats with AA were administered first pinosylvin (30 mg/kg body mass daily per os), second carnosine (150 mg/kg body mass daily per os) in monotherapy for a period of 28 days. Further, rats with AA were administered methotrexate (0.3 mg/kg body mass 2-times weekly per os), and a combination of methotrexate+carnosine, with the carnosine dose being the same as in the previous experiment. Parameters, i.e. changes in hind paw volume and arthritic score were determined in rats as indicators of destructive arthritis-associated clinical changes. Plasmatic levels of TBARS and lag time of Fe2+- induced lipid peroxidation (tau-FeLP) in plasma and brain were specified as markers of oxidation. Plasmatic level of CRP and activity of γ-glutamyltransferase (GGT) in spleen and joint were used as inflammation markers. In comparison to pinosylvin, administration of carnosine monotherapy led to a significant decrease in the majority of the parameters studied. In the combination treatment with methotrexate+carnosine most parameters monitored were improved more remarkably than by methotrexate alone. Carnosine can increase the disease-modifying effect of methotrexate treatment in rat AA.
Rado Nosáľ, Katarína Drábiková, Viera Jančinová, Tatiana Mačičková, Jana Pečivová, Tomáš Perečko and Juraj Harmatha
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.
Arád Kósa, L’ubica Stuchlíková, Wojciech Dawidowski, Juraj Jakuš, Beata Sciana, Damian Radziewicz, Damian Pucicki, Ladislav Harmatha, Jaroslav Kováč and Marek Tłaczala
In this paper authors present the results of identification of emission and capture processes in tandem solar cell structures based on quaternary InGaAsN semiconductor alloys by DLTFS (Deep Level Transient Fourier Spectroscopy) and by ana- lytical evaluation processes. The energies of five trap levels ET1=0.77 eV, ET2=0.47 eV, ET3=0.64 eV, HT1=0.62 eV and HT2=0.53 eV were identified with reliable accuracy. These values were obtained by available analytical procedures, verified by simulations and confirmed by reference structures with basic layer types and compared with possible reference trap data. Native structural defects in GaAs were stated as the origin of these deep energy levels