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1
Content available remote Activity of selected aromatic amino acids in biological systems
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EN
Besides the structural function in proteins, aromatic amino acids are precursors of many important biological compounds essential for normal functioning of the human organism. Many of these compounds may be used as markers for identification of specific pathological states. Comprehensive knowledge about the metabolism of aromatic amino acids and mechanisms of action of their metabolites made it possible to develop effective treatments for many disorders. However, it should not be forgotten that in some pathological conditions, these compounds could not only be involved in the pathogenesis of many disease entities but could also be used as an important tool in prediction of many diseases. This paper contains a review of published literature on aromatic amino acids in the context of physiological processes of the human body and chosen social disorders, such as cancers; psychiatric disorders: depression, anxiety states, schizophrenia, bipolar affective disorders; neurodegenerative, and cardiovascular diseases; chronic kidney insufficiency or diabetes.
EN
Second messengers involved in the signal transduction pathway leading to induction of the plasminogen activator inhibitor (PAI-1) have not yet been well characterized. This study focuses on the mechanisms of regulation of PAI-1 expression by reactive oxygen species (ROS) in human endothelial cells. Inhibition of the tumor necrosis factor α (TNFα)-induced expression of PAI-1 by antioxidant N-acetyl-L-cysteine (NAC) indicated redox-sensitive mechanisms involved in the signalling pathway. Because TNFα induces PAI-1 production in endothelial cells, and NAC attenuated this response, we attempted to investigate the possible involvement of ROS in the activation of PAI-1 by TNFα. Upregulation of PAI-1 expression in endothelial cells by the stimulation with TNFα (50ng/ml) or H2O2 (10-200µM), observed by measurement of the antigen and mRNA levels, was reversed in the presence of NAC (20mM). The stimulatory effect of ROS was detected also at the level of the PAI-1 promoter in endothelial cells transfected with plasmid p800 LUC containing a PAI-1 promoter fragment (+71 to -800). The PAI-1 promoter activity was increased in the presence of ROS, and was suppressed by up to 75% in the presence of antioxidants [1], On the basis of this study we can conclude that reactive oxygen species play an important role in a cytokine-induced activation of PAI-1 expression, and may act as a signal transduction messenger.
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Content available remote NF-κB signaling pathway and free radical impact
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The activation of NF-κB transcription factor is critical for a wide range of processes such as immunity, inflammation, cell development, growth and survival. It is activated by a variety of stimuli including cytokines, ionizing radiation and oxidative stress. Redox modulations of NF-κB pathway have been widely demonstrated. Studies carried out during last years have advanced our knowledge about possible connections between NF-κB pathway and the impact of free radicals. This review is an endeavor to gather recent results focused on this issue, although an important question, whether oxidative stress plays a physiological role in NF-κB activation, seems to be still unanswered.
EN
The budding yeast Saccharomyces cerevisiae is a well studied unicellular eukaryotic organism the genome of which has been sequenced. The use of yeast in many commercial systems makes its investigation important not only from basic, but also from practical point of view. Yeast may be grown under both aerobic and anaerobic conditions. The investigation of the response of eukaryotes to different kinds of stresses was pioneered owing to yeast and here we focus mainly on the so-called oxidative stress. It is a result of an imbalance between the formation and decomposition of reactive oxygen species increasing their steady-state concentration. Reactive oxygen species may attack any cellular component. In the present review oxidation of proteins in S. cerevisiae is analyzed. There are two connected approaches to study oxidative protein modification - characterization of the overall process and identification of individual oxidized proteins. Because all aerobic organisms possess special systems which defend them against reactive oxygen species, the involvement of so-called antioxidant enzymes, particularly superoxide dismutase and catalase, in the protection of proteins is also analyzed.
EN
Purpose. In adult liver transplant recipients, coronary artery disease and congestive heart failure are significant cause of morbidity and mortality. This may be attributed to the long-term immunosuppressive treatment, mostly with calcineurin inhibitors and steroids, which in long-term may be associated with hyperlipidemia, oxidative stress and cardiovascular complications. Since such data for children is sparse, the aim of this study was to assess the lipid and oxidative stress markers after pediatric liver transplantation (LTx). Method. We performed prospective analysis of 74 children, at the median age of 7.9 (2.8-11.6) years, 3.2 (1.2-4.3) years after LTx. We assessed the BMI Z-scores, cholesterol fractions (LDLc, HDLc, VLDLc), triglicerides, apolipoproteins (ApoAI, ApoB, ApoE), LCAT, insulin resistance by HOMA-IR and markers of oxidative stress and atherosclerosis: glutathione (GSH), glutathione peroxidase (GPx), asymmetrical dimethyl arginine (ADMA) and oxidized low-density lipoprotein (oxyLDL). At baseline, the results were compared with a healthy age-and-sex matched control group. After 3.1±0.3 year follow-up we repeated all investigations and compared them with the baseline results. RESULTS. At the baseline, we investigated 74 patients 3.2 (1.2-4.3) years after LTx, at the median age of 7.9 (2.8-11.6) years. The prevalence of overweight or obesity (BMI >85th percentile) was 23% and was more common in girls (24% vs 20%). Fourteen patients had TCH >200 mg%, 9 patients had LDLc >130 mg% and TG were at normal levels in all patients. Compared to the controls, there were no significant differences in lipid profiles but we found decreased GSH (p<0.001) and GPx (p<0.001) which play role as an antioxidant defense. OS markers were higher in the study group: ADMA (p<0.001), and oxyLDL (p<0.0001). Insulin resistance by HOMA-IR was increased in the study group (p=0.0002) but fasting glucose remained within normal ranges in all patients. After 3.1-year follow-up, the BMI >95th and >85Th percentile was present in 8% and 14% respectively. ADMA and oxyLDL decreased, whilst GSH and GPx increased when compared to the baseline. There was also significant decrease in apoB and Lp(a). Conclusion. Children after LTx had normal lipid profiles when compared to controls, however there is a tendency for hypercholesterolemia and obesity, which may play a role in cardiovascular complications in the future. Some markers of oxidative stress were increased after LTx, however further investigations are required to establish its clinical significance.
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Content available remote Expression and activity of superoxide dismutase isoenzymes in colorectal cancer
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The aim of the study was an evaluation of changes in protein level and activity of SOD isoenzymes, and the participation of AP-1 and NF-κB in subsequent stages of colorectal cancer development. Studies were conducted on 65 colorectal cancers. Controls were unchanged colon regions. Activity of SOD isoenzymes, lipid peroxidation level (TBARS), and protein level of SOD1, SOD2, AP-1 and NF-κB were determined. We found that the protein level and activity of SOD isoenzymes and protein level of AP-1 and NF-κB change in subsequent stages of clinical advancement of colorectal cancer, according to UICC (I-IV), and in grades of tumor cells differentiation (G1-G3). These results indicate adaptation of colorectal cancer cells to oxidative stress, and show that the observed changes of SOD activity and protein level depend on gradual progression of colorectal cancer, and suggest an impairment of processes regulated by AP-1 and NF-κB which are critical for tumor progression (proliferation, differentiation and apoptosis).
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Content available Oxidants and antioxidants of erythrocytes
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Erythrocytes contain reactive forms of oxygen (superoxide anion, hydrogen peroxide, hydroxyl radical) and reactive form of nitrogen (nitric oxide anion, S-nitrosothiols, peroxynitrite anion). Reactive oxygen species and reactive nitrogen species inactivate enzymatic (methemoglobin reductase, Cu, Zn-Superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic (glutathione, alpha-tocopherol, beta-carotene, ascorbate) antioxidants. Their quantity in erythrocytes increases in case of exposure to xenobiotics, in erythrocytes containing pathological hemoglobin, in erythrocytes with the enzymatic defects of the glycolytic or pentose cycle, in erythrocytes found in arterial and venous thrombi, and in the blood extravasated to tissues and body cavity. In such cases are observed in erythrocytes: structure modification of hemoglobin and membrane proteins, and lipids peroxidation. These processes cause changes of shape, decrease of flexibility, decrease of resistance to hemolysis, Heinz's bodies production and shorten the life span of red cells.
EN
Neutrophils form the first line of host defense against infections that combat pathogens using two major mechanisms, the phagocytosis or the release of neutrophil extracellular traps (NETs). The netosis (NET formation) exerts additional, unfavorable effects on the fitness of host cells and is also involved at the sites of lung infection, increasing the mucus viscosity and in the circulatory system where it can influence the intravascular clot formation. Although molecular mechanisms underlying the netosis are still incompletely understood, a role of NADPH oxidase that activates the production of reactive oxygen species (ROS) during the initiation of NETs has been well documented. Since several commonly used drugs can affects the netosis, our current study was aimed to determine the effects of selected mucolytic, anti-inflammatory and cardiovascular drugs on NET formation, with a special emphasis on ROS production and NADPH oxidase activity. The treatment of neutrophils with N-acetylcysteine, ketoprofen and ethamsylate reduced the production of ROS by these cells in a dose-dependent manner. NET formation was also modulated by selected drugs. N-acetylcysteine inhibited the netosis but in the presence of H2O2 this neutrophil ability was restored, indicating that N-acetylcysteine may influence the NET formation by modulating ROS productivity. The administration of ethamsylate led to a significant reduction in NET formation and this effect was not restored by H2O2 or S. aureus, suggesting the unexpected additional side effects of this drug. Ketoprofen seemed to promote ROS-independent NET release, simultaneously inhibiting ROS production. The results, obtained in this study strongly suggest that the therapeutic strategies applied in many neutrophil-mediated diseases should take into account the NET-associated effects.
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Content available remote A study of free radical chemistry: their role and pathophysiological significance
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EN
Oxygen is one of the most important molecules on Earth mainly because of the biochemical symmetry of oxygenic photosynthesis and aerobic respiration that can maintain homeostasis within our planet's biosphere. Oxygen can also produce toxic molecules, reactive oxygen species (ROS). ROS play a dual role in biological systems, since they can be either harmful or beneficial to living systems. They can be considered a double-edged sword because at moderate concentrations, nitric oxide (NO•), superoxide anion, and related reactive oxygen species play an important role as regulatory mediators in signalling processes. Many of the ROS-mediated responses actually protect the cells against oxidative stress and re-establish "redox homeostasis". On the other hand, overproduction of ROS has the potential to cause damage. In the recent decades, ROS has become a focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence from research on several diseases shows that oxidative stress is associated with the pathogenesis of diabetes mellitus, obesity, cancer, cardiovascular diseases, inflammation, ischaemia/reperfusion injury, obstructive sleep apnea, neurodegenerative disorders, hypertension and ageing.
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The paper reviews selected examples of the bystander effect, such as clonogenic survival decrease, chromosomal aberrations and mutations. The similarities and differences between the biological effects in directly targeted and bystander cells are briefly discussed. Also reviewed are the experimental data which support the role of reactive oxygen species (ROS), especially *O2-, as mediators of the bystander effect. Endogenously generated ROS, due to activation of NAD(P)H oxidases, play a key role in the induction of DNA damage in bystander cells. All the observed effects in bystander cells, such as alterations in gene expression patterns, chromosomal aberrations, sister chromatid exchanges, mutations, genome instability, and neoplastic transformation are the consequence of DNA damage.
EN
Background: Head and neck neoplasms stand for 6% of all malignant neoplasms worldwide. Chemotherapy has limited use due to the biological properties of the tumor (in the majority of cases moderately and poorly differentiated squamous cell carcinoma). The fundamental molecule used in treatment is cisplatin and its derivates, that can be associated with fluorouracil. The new chemotherapeutic agents are not in common use during the treatment of head and neck malignancies. However, the use of low molecular weight complexes Pd (II) carries the potential of being more effective in therapy. Material and Methods: Fifty-one patients, 30 men and 21 women (aged 52.9 ± 12.1 years) with head and neck cancer were included in the study. Fifty-one healthy subjects, 31 men and 20 women, (aged 54.1 ± 14.7 years) years formed the control group. Antioxidant enzymes, superoxide dismutase, and catalase activities in erythrocytes were examined. Results: An increased level of antioxidant enzymes was seen in the blood samples from patients with head and neck cancer after incubation with Pd (II) complex. In the group we obtained a statistically significant result p = <0.001. Discussion: That project may contribute to the development of new, more efficient head and neck cancer treatment strategies. In our opinion, the results can be used in the future to develop a valuable prognostic marker of the disease. This is important because the initial phase of cancer is asymptomatic. The search for factors involved in pathogenesis translates into economic benefits and makes therapy more effectiveness through the reduction of treatment expenses.
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Simulated maxillary sinusitis was observed in guinea pigs following the surgical incision in superior cervical sympathetic ganglion. Additionally, toxic hepatitis development was stimulated after exposure to tetrachlormethane in experimental animals. The treated and control animals were observed for three months. A significant increase in the content of reactive oxygen species (ROS) in neutrophils and lymphocytes was noted in artificially developed sinusitis. The ROS values were slightly higher in the case of combined experimental sinusitis and toxic hepatitis. Based on the obtained data, the role of ROS in the development of sinusitis was discussed.
EN
Introduction: Nanoparticles (NPs) have been proven to enhance radiotherapy doses as radiosensitizers. The introduction of coating materials such as polyethylene glycol (PEG) to NPs could impact the NPs’ biocompatibility and their effectiveness as radiosensitizers. Optimization of surface coating is a crucial element to ensure the successful application of NPs as a radiosensitizer in radiotherapy. This study aims to investigate the influence of bismuth oxide NPs (BiONPs) coated with PEG on reactive oxygen species (ROS) generation on HeLa cervical cancer cell line. Material and methods: Different PEG concentrations (0.05, 0.10, 0.15 and 0.20 mM) were used in the synthesis of the NPs. The treated cells were irradiated with 6 and 12 MeV electron beams with a delivered dose of 3 Gy. The reactive oxygen species (ROS) generation was measured immediately after and 3 hours after irradiation. Results: The intracellular ROS generation was found to be slightly influenced by electron beam energy and independent of the PEG concentrations. Linear increments of ROS percentages over the 3 hours of incubation time were observed. Conclusions: Finally, the PEG coating might not substantially affect the ROS generated and thus emphasizing the functionalized BiONPs application as the radiosensitizer for electron beam therapy.
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Background: Head and neck neoplasms stand for 6% of all malignant neoplasms worldwide. Chemotherapy has limited use due to the biological properties of the tumor (in the majority of cases moderately and poorly differentiated squamous cell carcinoma). The fundamental molecule used in treatment is cisplatin and its derivates, that can be associated with fluorouracil. The new chemotherapeutic agents are not in common use during the treatment of head and neck malignancies. However, the use of low molecular weight complexes Pd (II) carries the potential of being more effective in therapy. Material and Methods: Fifty-one patients, 30 men and 21 women (aged 52.9 ± 12.1 years) with head and neck cancer were included in the study. Fifty-one healthy subjects, 31 men and 20 women, (aged 54.1 ± 14.7 years) years formed the control group. Antioxidant enzymes, superoxide dismutase, and catalase activities in erythrocytes were examined. Results: An increased level of antioxidant enzymes was seen in the blood samples from patients with head and neck cancer after incubation with Pd (II) complex. In the group we obtained a statistically significant result p = <0.001. Discussion: That project may contribute to the development of new, more efficient head and neck cancer treatment strategies. In our opinion, the results can be used in the future to develop a valuable prognostic marker of the disease. This is important because the initial phase of cancer is asymptomatic. The search for factors involved in pathogenesis translates into economic benefits and makes therapy more effectiveness through the reduction of treatment expenses.
EN
Candida species are associated with an increasing number of life-threatening infections (candidiases), mainly due to the high resistance of these yeast-like fungi to antifungal drugs and oxidative stress. Recently, thiamine (vitamin B1) was found to alleviate stress responses in Saccharomyces cerevisiae; however, thiamine influence on defense systems in pathogenic fungi has never been investigated. The current work was aimed to elucidate the role of thiamine in stress reactions of C. albicans, C. glabrata, C. tropicalis and C. dubliniensis, subjected to hydrogen peroxide treatment. As compared to S. cerevisiae, Candida strains exposed to oxidative stress showed: (i) a much higher dependence on exogenous thiamine; (ii) an increased demand for thiamine diphosphate (TDP) and TDP-dependent enzyme, transketolase; (iii) no changes in gene expression of selected stress markers - superoxide dismutase and catalase - depending on thiamine availability in medium; (iv) a similar decrease of reactive oxygen species (ROS) generation in the presence of thiamine. Moreover, the addition of therapeutic doses of thiamine to yeast culture medium revealed differences in its accumulation between various Candida species. The current findings implicate that the protective action of thiamine observed in S. cerevisiae differs significantly form that in pathogenic Candida strains, both in terms of the cofactor functions of TDP and the effects on fungal defense systems.
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WSTĘP: Choroba zwyrodnieniowa stawów kolanowych (gonartroza – GA) należy do najczęstszych schorzeń narządu ruchu, a ból i ograniczenie ruchomości kolana są najdotkliwiej odbieranymi przez pacjentów objawami zmian zwyrodnieniowych. Celem pracy było sprawdzenie, czy podanie dostawowe preparatu kwasu hialuronowego wpływa na funkcje stawu kolanowego, wybrane parametry układu antyoksydacyjnego i natężenie stresu oksydacyjnego we krwi u pacjentów z gonartrozą. MATERIAŁ I METODY: Grupa badana 1K obejmowała 96 pacjentów z chorobą zwyrodnieniową stawu kolanowego, którym podano kwas hialuronowy do jednego stawu kolanowego, natomiast do grupy badanej 2K włączono 33 pacjentów, którym podano kwas hialuronowy do obu stawów kolanowych. Badanie prowadzono przez 40 tygodni według ustalonego protokołu. Oznaczono całkowity status oksydacyjny (TOS) osocza, zawartość grup sulfhydrylowych (SH) w surowicy, aktywność katalazy (CAT) w erytrocytach, aktywność dysmutazy ponadtlenkowej (SOD) w osoczu i erytrocytach, aktywność peroksydazy glutationowej (GPx) w erytrocytach. WYNIKI: Po leczeniu wiskosuplementacyjnym odnotowano zmniejszenie nasilenia bólu oraz poprawę w badanych skalach VAS i HHS, przy czym nieco większą poprawę stwierdzono w przypadku zajęcia jednego kolana. Po leczeniu dostawowym kwasem hialuronowym stwierdzono znamienny spadek aktywności SOD oraz CAT a wzrost aktywności GPx, wzrost stężenia grup SH w obu grupach oraz spadek stężenia TOS. WNIOSKI: Wiskosuplementacja w chorobie zwyrodnieniowej stawu kolanowego istotnie redukuje ból kolana i poprawia jego funkcje oraz wywołuje korzystne zmiany w układzie antyoksydacyjnym krwi. Efekt leczenia jest porównywalny zarówno w przypadku podawania preparatu kwasu hialuronowego do jednego, jaki i do obu stawów kolanowych.
PL
INTRODUCTION: Osteoarthritis of the knee (gonarthritis – GA) is one of the most common musculoskeletal disorders. Pain and limitation of joint movement are the most constant and troublesome symptoms of the joint pathology. The aim of the study was to examine viscosupplementation therapy with hyaluronic acid. MATERIAL AND METHODS: 96 patients were administered hyaluronic acid unilaterally (the 1K group), while 33 patients were administered hyaluronic acid bilaterally (the 2K group) in a 40-day cycle. The stage of the disease was assessed based on medical history, physical examination and a questionnaire survey. Analysis of the following parameters was performed: serum level of sulfhydryl groups (SH), total oxidant status (TOS), catalase activities (CAT) and glutathione peroxidase (GPx) in erythrocytes and superoxide dismutase activity (SOD) in plasma and erythrocytes. RESULTS: Viscosupplementation resulted in pain reduction and improvement in the HHS score. The SOD and CAT activities were significantly decreased, while GPx activity as well as the SH level significantly increased in both the examined groups. In addition the TOS values significantly decreased. CONCLUSION: Viscosupplementation therapy with hyaluronic acid significantly reduces pain of the knee joint, improves its function and has a beneficial effect on the pro/antioxidant balance in the blood of patients diagnosed with GA. The effects of uni- and bilateral administration of hyaluronic acid are similar.
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