Sol-Gel Synthesis of Silica-Poly (Vinylpyrrolidone) Hybrids with Prooxidant Activity and Antibacterial Properties.

The present work deals with the sol-gel synthesis of silica-poly (vinylpyrrolidone) hybrid materials. The nanohybrids (Si-PVP) have been prepared using an acidic catalyst at ambient temperature. Tetramethyl ortosilane (TMOS) was used as a silica precursor. Poly (vinylpyrrolidone) (PVP) was introduced into the reaction mixture as a solution in ethanol with a concentration of 20%. The XRD established that the as-prepared material is amorphous. The IR and 29Si MAS NMR spectra proved the formation of a polymerized silica network as well as the hydrogen bonding interactions between the silica matrix and OH hydrogens of the silanol groups. The TEM showed spherical particle formation along with increased agglomeration tendency. The efficacy of SiO2/PVP nanoparticles as a potential antimicrobial agent against a wide range of bacteria was evaluated as bacteriostatic, using agar diffusion and spot tests. Combined effects of hybrid nanomaterial and antibiotics could significantly reduce the bactericidal concentrations of both the antibiotic and the particles, and they could also eliminate the antibiotic resistance of the pathogen. The registered prooxidant activity of the newly synthesized material was confirmative and explicatory for the antibacterial properties of the tested substance and its synergetic combination with antibiotics. The effect of new hybrid material on Crustacea Daphnia magna was also estimated as harmless under concentration of 0.1 mg/mL.

Susceptibility of SARS COV-2 nucleocapsid and spike proteins to reactive oxygen species and role in inflammation.

Chemiluminescence was used to test the susceptibility of the SARS-CoV-2 N and S proteins to oxidation by reactive oxygen species (ROS) at pH 7.4 and pH 8.5. The Fenton's system generates various ROS (H2O2, OH, -OH, OOH). All proteins were found to significantly suppress oxidation (the viral proteins exhibited 25-60% effect compared to albumin). In the second system, H2O2 was used both as a strong oxidant and as a ROS. A similar effect was observed (30-70%); N protein approached the effect of albumin at physiological pH (∼45%). In the O2.--generation system, albumin was most effective in the suppression of generated radicals (75%, pH 7.4). The viral proteins were more susceptible to oxidation (inhibition effect no more than 20%, compared to albumin). The standard antioxidant assay confirmed the strong antioxidant capacity of both viral proteins (1.5-1.7 fold higher than albumin). These results demonstrate the effective and significant inhibition of ROS-induced oxidation by the proteins. Obviously, the viral proteins could not be involved in the oxidative stress reactions during the course of the infection. They even suppress the metabolites involved in its progression. These results can be explained by their structure. Probably, an evolutionary self-defense mechanism of the virus has been developed.

Prooxidant and antimicrobic effects of iron and titanium oxide nanoparticles and thalicarpine.

The aim is to evaluate the prooxidant and antimicrobial effects of Fe3O4 and TiO2 nanoparticles and thalicarpine by luminescent and standard microbiological assays. Their effect on the kinetics of free-radical oxidation reactions (at pH 7.4 and pH 8.5) is studied in the following model systems, using activated chemiluminescence: chemical, with Fenton's reagent (H2O2-FeSO4)-for the generation of hydroxyl radicals (.OH); chemical, with oxidant hydrogen peroxide (H2O2); chemical (NAD.H-PhMS), for the generation of superoxide radicals (O2.-). Fe3O4 nanoparticles exhibit highly pronounced antioxidant properties; TiO2 nanoparticles exhibit mild to moderate prooxidant properties at neutral and alkaline conditions. Those properties are tested by the chemiluminescent method for the first time. Thalicarpine and its combination with TiO2 nanoparticles exhibit pronounced antioxidant activities at pH 8.5 which are lost and transformed into well-presented prooxidant effects at pH 7.4. That is a result-supported proof on the observed typical properties of thalicarpine and TiO2, namely antibacterial, organic-preserving and anti-pathogenic activities. The antimicrobial effect is tested on Gram-positive and Gram-negative bacteria: two strains of Escherichia coli, Bacillus cereus 1095 and Staphylococcus aureus. All bacteria are destroyed after the application of TiO2, but not Fe3O4 nanoparticles, showing their antibacterial effect. Thalicarpine, in combination with TiO2, showed even synergetic antibacterial effect.

Antibacterial effect of TiO2 :Cu:Ag thin coatings on Pseudomonas strain measured by microbiological and ATP assays.

The aim of this study is to investigate the antimicrobial properties of nanocomposite thin TiO2 :Cu:Ag films on Pseudomonas putida as a natural isolate and an opportunistic pathogen. Several different methods were used to compare the antibacterial effect of thin TiO2 :Cu:Ag layers obtained by radiofrequency magnetron sputter deposition against P. putida: optical density of the bacterial suspension, most probable number of survived cells, dehydrogenase activity inhibition, scanning electron microscopy images, atomic flame absorption spectroscopy, and adenosine triphosphate (ATP) luminescent assay. Optical density measurements and most probable plate count were in agreement and showed a strong bactericidal effect of the as-deposited and only bacteriostatic effect of the annealed coatings with the same metal content on tested bacteria. As the metal quantity in the medium rises during the first hour of the experiment, it could be suggested that this is the main reason for cell death. ATP-luminescent assay showed up to 18-fold reduction of the signal. It was compared with other microbiological and biochemical assays to prove the strong antibacterial effect of nanocomposite thin TiO2 :Cu:Ag coatings with the possibilities of medical applications. Protection of medical devices against infections is a significant current challenge raised by an increasing number of medical devices-associated infections and microbial resistance to conventional antibiotic and multidrug treatments. Deposition of antimicrobial coatings is one of the current approaches to mitigate the problem.

Synthesis and physicochemical properties of novel lophine derivatives as chemiluminescent in vitro activators for detection of free radicals.

The overproduction of free radicals and reactive oxygen species (ROS) has been proved as a basic damage mechanism and cause for oxidative stress. Their measurement is often hindered by the low signal. This could be resolved with the application of luminescent probes (lophines, luminol, lucigenin, etc.). The focus of this study is to synthesize and describe the spectral properties and physicochemical characteristics of lophine and its derivatives as new chemiluminescent in vitro activators. The prepared luminophores are analogues of lophine. Their absorption maxima are in the range 329-340 nm, with good-to-high extinction coefficients. Their spectral properties are measured in methanol and buffer solutions with pH 3.5, 7.4 and 8.5. Same conditions were applied in the systems for chemiluminescent assay in vitro: (1) Fenton's (Fe(2+)+H2O2) for the generation of ·OH and -OH species, (2) Hydrogen peroxide (H2O2), (3) Iron (II) sulfate (FeSO4), (4) Glutathione-peroxidase, monitoring the deactivation of H2O2, (5) Ascorbic acid-Fenton's reagent: Vit.C appears a strong oxidant, generating free-radical products when applied in higher than physiological concentrations, (6) Reduced α-nicotinamide adenine dinucleotide (NADH)-phenazine methosulfate-for the generation of superoxide radicals (O2 (·-)). Lophine and all novel compounds do not alter the kinetics, except of the dimethyl amino substituted derivative (4-(3a,11b-dihydro-1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)-N,N-dimethylaniline) in the glutathione-peroxidase system, at pH 8.5. Same derivative showed a comparable or higher activity than Lucigenin and Rhodamine 6G. In neutral and acidic medium, in the Fenton's system, Rhodamine 6G was the most appropriate probe. In alkaline pH and oxidant H2O2, Lucigenin induced a signal twice as strong as the signal compared to all other activators.

The effect of resistin on the redox state of breast cancer cells.

PURPOSE: Resistin is an inflammatory cytokine secreted mostly by adipocytes and immune cells that plays a role in the development of insulin resistance, diabetes, and cancer. We hypothesized that resistin's inflammatory activity influences the free radical and oxidative stress pathways. METHODS: We used human breast carcinogenic (MCF-7 and MDA-MB-231) and non-carcinogenic (MCF-10A) cells in this investigation and correlated the absorbed resistin concentration with the change in oxidative stress (TBARS, carbonated proteins) and antioxidant activity (Antioxidant Capacity, SuperOxideDismutase, CATalase, Glutathione Peroxidase). RESULTS: Resistin was substantially more effective as a prooxidant at lower (12.5 ng/ml) concentrations, than at higher concentrations (25.0 ng/ml). Vitamin C did not appear to be an effective oxidative stress protector at antioxidant concentrations of 5.10-4 M. Leptin, at 100 ng/ml, did not result in conclusive oxidative stress or antioxidant defence stimulation, as expected. CONCLUSION: Taken together, the findings support resistin's role as a non-oxidative stress marker and a metabolic signaling molecule.

Investigation of Biological and Prooxidant Activity of Zinc Oxide Nanoclusters and Nanoparticles.

Zinc oxide (ZnO) nanomaterials offer some promising antibacterial effects. In this study, a new form of ZnO is synthesized, named ZnO nanocluster bars (NCs). Herein, ZnO NCs, ZnO nanoparticles (NPs), ZnO coated with silica (ZnO-SiOA, ZnO-SiOB), and SiO2 NPs were prepared, characterized, and their antimicrobial and prooxidant activity were tested. The prooxidant activity of all nanomaterials was studied according to free-radical oxidation reactions (pH 7.4 and pH 8.5) in chemiluminescent model systems. Each form of new synthesized ZnO nanomaterials exhibited a unique behavior that varied from mild to strong prooxidant properties in the Fenton`s system. ZnO NPs and ZnO NCs showed strong antibacterial effects, ZnO-SiOA NPs did not show any antibacterial activity representing biocompatibility. All tested NMs also underwent oxidation by H2O2. ZnO NCs and ZnO NPs exhibited strong oxidation at pH 8.5 in the O2-. generating system. While, SiO2, ZnO-SiOA andZnO-SiOB possessed pronounced 60-80% antioxidant effects, SiO2 NPs acted as a definitive prooxidant which was not observed in other tests. ZnO NCs are strong oxidized, assuming that ZnO NCs provide a slower release of ZnO, which leads to having a stronger effect on bacterial strains.  Thus, ZnO NCs are an important antibacterial agent that could be an emergent replacement of traditional antibiotics.

Antiviral, Cytotoxic and Antioxidant Effects of Tanacetum Vulgare L. Crude Extract In Vitro.

INTRODUCTION: Due to the high prevalence of viral infections having no specific treatment and the constant emergence of resistant viral strains, searching for effective antiviral compounds is crucial. The present study explores in vitro the antiviral activity of ethanolic extract from aerial parts of. AIM: The aim of the current study was to evaluate antiviral activity of ethanolic extract from herbaceous plant. MATERIALS AND METHODS: The crude aqueous ethanolic extract from aerial parts of. RESULTS: The results show that the extract has the lowest toxicity on the MDBK cell line and similar cytotoxicity in Hep-2, whereas in the MDCK cells it has more than twice the highest toxicity. Testing the antiviral activity of. CONCLUSION: The crude extract from aerial parts of the medicinal plant.

Combined efficacy of oseltamivir, isoprinosine and ellagic acid in influenza A(H3N2)-infected mice.

Influenza pathogenesis comprises a complex cascade of impaired cellular processes resulting from the viral replication and exaggerated immune response accompanied by reactive oxygen species (ROS) burst and oxidative stress, destructing membranous structures and tissues. By classical virological and biochemical methods we compared and evaluated the therapeutic effects of 2.5mg/kg/day of the antiviral drug - oseltamivir (OS), 500mg/kg/day of the immune modulator - isoprinosine (IP) and 500mg/kg/day of the antioxidant agent ellagic acid (EA) with a focus on their combined activities in influenza H3N2 virus-infected mice. The survival, lung pathology and titers, as well as the oxidative stress biomarker thiobarbituric acid reactive substances (TBARS) in the lungs, liver and blood plasma, correlated to the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione reductase (GR) were assessed. We found that the viral inhibitor applied together with the immune modulator and the antioxidant exhibited strong therapeutic effects on the survival of the influenza-challenged mice. That effect was mostly pronounced for the triple combination - protection index (PI) of 75.2%, mean survival time (MST) extended by 5.8 days compared to the PBS control and significant reduction of the lung titers by 1.38 Δlg; 2.3 scores lower lung pathology and 8 times reduction of the accumulated TBARS in the lungs and liver on the 5-th day p.i. The enzymatic assays revealed that this combination demonstrated very good protection against the damaging superoxide radicals (83% efficiency of SOD, in comparison to healthy controls 100%). The double combinations of OS with IP and EA also showed protective effects according to the virological analysis - PI of 53.1% and 54.5%. Ten times higher GR activity was observed when the combination EA+OS and monotherapy of EA were applied (96% in comparison to healthy controls 100%). The best antioxidant effect in blood plasma was observed in the EA+IP group - 4 times reduction in the TBARS-content compared to infected controls but it did not have any efficacy on the survival and lung injury.

Effects of rutin and quercetin on monooxygenase activities in experimental influenza virus infection.

The aim of this work is to study the effect of the flavonoids rutin and quercetin on hepatic monooxygenase activities in experimental influenza virus infection (EIVI). EIVI causes oxidative stress in the whole organism. This is confirmed by the rapidly increased concentrations of thiobarbituric reactive substances in influenza-infected mice: lungs - 290%; blood plasma - more than 320%; liver - 230%; brain - 50%. Although known for their antioxidant activities, rutin and quercetin exhibit prooxidant effect in healthy and antioxidant activity in influenza-infected animals. The pretreatment with both flavonoids (20 mg/kg b.w.) restores oxidative damage mostly in the target organ of the infection as well as in the liver of all infected mice (lungs: rutin - 30%, quercetin - 40%, combination - 45%; liver: rutin - 12%; quercetin - 40%; combination - 50%). As far as EIVI causes oxidative stress, toxicosis and inhibition of the hepatic monooxygenase activity, it is important to study the effects of rutin and quercetin on these systems. Both flavonoids induce the level of cytochrome P-450 (rutin - 13%, quercetin - 30%, combination - 22%) but inactivate NADPH-cytochrome c reductase, aminopyrine N-demethylase and analgin N-demethylase on the 5th day of EIVI. Probably, these flavonoids affect different components of the monooxygenase system. These effects could be explained with oxidative hepatic intoxication on the 5th critical day of EIVI as well as higher dose treatment. More data are needed on the antioxidant/prooxidant effects of rutin and quercetin, probably due to specific metabolic and physiological activities, chemical structure, etc.

Comparative study on the antioxidant capacities of synthetic influenza inhibitors and ellagic acid in model systems.

This study compares the antioxidant capacities in vitro of several synthetic and natural compounds applied and researched for influenza treatment - oseltamivir, isoprinosine, ellagic acid, vitamin E and vitamin C. Three chemical systems are utilized for the generation of reactive oxygen species (ROS) at pH 7.4 and pH 8.5: (1) Fenton's (Fe2++H2O2) for OH and -OH species (2) H2O2 (3) NADH-phenazinemethosulfat, for superoxide radicals (O2-). The kinetics was evaluated by lucigenin-enhanced chemiluminescence. The calculated constants of inhibition k7 describe the antioxidant capacity at the moment of oxidative burst. Their values do not necessarily correspond to the calculated total antioxidant activity. The obtained results revealed that the synthetic anti-influenza drugs (oseltamivir and isoprinosine) as well as ellagic acid possess pronounced scavenging properties mostly against superoxide radicals, comparable and higher than that of traditional natural antioxidants. Quantitative analysis of the antioxidant effects of the examined synthetic substances was performed. The results compared the corresponding effect of the average physiological concentrations and the applied therapeutic antioxidant dose. With these experiments we registered new aspects of their therapeutic activities, due to antioxidant properties against hydroxyl, superoxide radicals and H2O2 oxidation.

Oxidative stress in children with kidney disease.

The aim of this work was to study the dynamics of oxidative stress in the blood and urine of children with kidney diseases: glomerulonephritis (GN), pyelonephritis (PN), renal failure (RF), and lower urinary tract infections (LUTI). The concentration of conjugated dienes is increased in blood: GN 4 times and RF up to 2 times; and extremely increased in urine: GN 12 times and RF 4 times. The concentration of thiobarbituric acid reactive substances in urine shows a similar trend: GN 7 times, PN 2 times, RF 1.5 times, and LUTI almost 3 times. Urine chemiluminescence is also increased: GN 5 times, PN and LUTI 3 times, and RF 6 times. Kidney disease leads to 2.5-fold inhibition of antioxidant catalase activity in blood and 10-fold in urine. Total antioxidant activity of urine is induced in all groups: GN 18 times, PN 2 times, RF 1.5 times, and almost 4 times in the LUTI group. Experimental data confirm that products of lipid peroxidation, intensity of chemiluminescence, and total and enzyme antioxidant capacity in combination with clinical parameters are a proper test for the dynamics of oxidative stress and markers of intoxication in children with inflammatory and immunological active parenchymal kidney disorders. These data could be helpful for the optimization of complex and effective antioxidant therapy of children with kidney disease.