Oxidative stress initiates, accompanies and contributes to the development of several human diseases and injuries, including ocular diseases. Reactive oxygen species (ROS) can generate oxidative stress via excessive ROS production and/or decreased physiologically occurring antioxidants. To replace these weakened antioxidants, substances with effective antioxidant properties are needed in order to suppress oxidative stress and enable healing. Molecular hydrogen (H2) is very suitable for this purpose due to its unique properties. H2 is the only antioxidant that crosses the blood-brain and blood-ocular barriers. It quickly penetrates through tissue due to its small molecular size and effectively removes ROS, mainly hydroxyl radicals and peroxynitrite. Apart from its antioxidant effects, H2 also displays anti-inflammatory, antiapoptotic, cytoprotective and mitohormetic properties. A significant advantage of H2 is its nontoxicity, even when applied at high concentrations. In this review, we present the results of studies utilising H2 in the treatment of ocular diseases involving oxidative stress. These results, obtained in experimental animals as well as in human clinical studies, show that the suppression of oxidative stress by H2 treatment leads to the prevention or improvement of ocular diseases. In severe degenerative diseases, H2 slows disease progression.
- MeSH
- lidé MeSH
- oční nemoci farmakoterapie patologie MeSH
- oxidační stres účinky léků MeSH
- vodík farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The storage time and storage temperature might affect stability of oxidative stress biomarkers, therefore, they have to be analyzed after long-term storage of serum samples. The stability of three biomarkers reflecting oxidative stress: reactive oxygen metabolites (ROM) for hydroperoxides, total thiol levels (TTL) for the redox status and biological antioxidant potency (BAP) for the antioxidant status, was investigated at several time points during 60 months of storage at -20 and -80 °C. Biomarkers ROM and BAP showed a very good stability during storage for 60 months at both temperatures. In addition, the correlation of the data after 60 months of storage compared with the starting data was very good with correlation coefficients >0.9. The TTL assay showed good results in serum samples stored at -80 °C, but not in samples stored at -20 °C. Serum samples for analysis of the set of oxidative stress biomarkers ROM, BAP and TTL can be stored up to 60 months at -80 °C. ROM and BAP can also be stored at -20 °C during this period. The present results are very important for the biomarker-related epidemiological studies that make use of biobanks with samples stored for many years and for new project planning, including sample storage conditions.
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- biologické markery krev MeSH
- lidé MeSH
- oxidační stres * MeSH
- sérum metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
A novel approach to the diazabicyclo[2.2.2]octane core of prenylated bridged diketopiperazine alkaloids is described by direct oxidative cyclizations of functionalized diketopiperazines mediated by ferrocenium hexafluorophosphate or the Mn(OAc)3•2H2O/Cu(OTf)2 system. Divergent reaction pathways take place depending on the substitution pattern of the substrates and the oxidation conditions such as temperature or the presence or absence of persistent radical TEMPO. For ester-substituted diketopiperazines, the ester group exerts a significant influence on the reaction outcome and stereochemistry of the radical cyclizations.
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- alkaloidy chemie MeSH
- cyklizace MeSH
- diketopiperaziny chemie MeSH
- molekulární struktura MeSH
- oxidace-redukce MeSH
- Publikační typ
- časopisecké články MeSH
The COST Action CM1201 "Biomimetic Radical Chemistry" has been active since December 2012 for 4 years, developing research topics organized into four working groups: WG1 - Radical Enzymes, WG2 - Models of DNA damage and consequences, WG3 - Membrane stress, signalling and defenses, and WG4 - Bio-inspired synthetic strategies. International collaborations have been established among the participating 80 research groups with brilliant interdisciplinary achievements. Free radical research with a biomimetic approach has been realized in the COST Action and are summarized in this overview by the four WG leaders.
- MeSH
- biomimetika metody MeSH
- lidé MeSH
- volné radikály chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Endothelial dysfunction characterized by decreased nitric oxide (NO) bioavailability is the first stage of coronary artery disease. It is known that one of the factors associated with an increased risk of coronary artery disease is a high plasma level of uric acid. However, causative associations between hyperuricaemia and cardiovascular risk have not been definitely proved. In this work, we tested the effect of uric acid on endothelial NO bioavailability. Electrochemical measurement of NO production in acetylcholine-stimulated human umbilical endothelial cells (HUVECs) revealed that uric acid markedly decreases NO release. This finding was confirmed by organ bath experiments on mouse aortic segments. Uric acid dose-dependently reduced endothelium-dependent vasorelaxation. To reveal the mechanism of decreasing NO bioavailability we tested the effect of uric acid on reactive oxygen species production by HUVECs, on arginase activity, and on acetylcholine-induced endothelial NO synthase phosphorylation. It was found that uric acid increases arginase activity and reduces endothelial NO synthase phosphorylation. Interestingly, uric acid significantly increased intracellular superoxide formation. In conclusion, uric acid decreases NO bioavailability by means of multiple mechanisms. This finding supports the idea of a causal association between hyperuricaemia and cardiovascular risk.
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- acetylcholin farmakologie MeSH
- arginasa metabolismus MeSH
- buněčné linie MeSH
- cévní endotel metabolismus MeSH
- down regulace MeSH
- endoteliální buňky pupečníkové žíly (lidské) MeSH
- fosforylace MeSH
- hyperurikemie metabolismus MeSH
- kyselina močová krev chemie metabolismus MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nemoci koronárních tepen metabolismus MeSH
- oxid dusnatý biosyntéza metabolismus MeSH
- reaktivní formy kyslíku chemie metabolismus MeSH
- superoxidy metabolismus MeSH
- synthasa oxidu dusnatého, typ III metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The aminopyrimidine structural motif can be found in diverse biologically active compounds. This study aimed to describe the antioxidant activity of a series of di- and tri-substituted 5-aminopyrimidines using in vitro (TEAC, LPO) and cell-based assays. 2,4,6-trisubstituted 5-aminopyrimidines displayed the highest activity in the TEAC and LPO assays whereas compounds with protected 5-aminogroup were active in the cellular assay. This is most likely because of their better membrane permeability and intracellular metabolic activation. In summary, we have identified the antioxidant activity of a series of substituted 5-aminopyrimidines and their potential prodrugs which may have implications in the treatment of oxidative stress-related diseases.
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- aminy chemická syntéza chemie farmakologie MeSH
- antioxidancia chemická syntéza chemie farmakologie MeSH
- buňky Hep G2 MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- oxidace-redukce MeSH
- peroxidace lipidů účinky léků MeSH
- pyrimidiny chemická syntéza chemie farmakologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Oxidatively damaged DNA is implicated in various diseases, including neurodegenerative disorders, cancer, diabetes, cardiovascular and inflammatory diseases as well as aging. Several methods have been developed to detect oxidatively damaged DNA. They include chromatographic techniques, the Comet assay, (32)P-postlabelling and immunochemical methods that use antibodies to detect oxidized lesions. In this review, we discuss the detection of 8-oxo-7,8-dihydro-29-deoxyguanosine (8-oxodG), the most abundant oxidized nucleoside. This lesion is frequently used as a marker of exposure to oxidants, including environmental pollutants, as well as a potential marker of disease progression. We concentrate on studies published between the years 2000 and 2011 that used enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry to detect 8-oxodG in humans, laboratory animals and in cell lines. Oxidative damage observed in these organisms resulted from disease, exposure to environmental pollutants or from in vitro treatment with various chemical and physical factors.
- MeSH
- biologické markery analýza MeSH
- deoxyguanosin analogy a deriváty analýza MeSH
- DNA analýza chemie MeSH
- ELISA MeSH
- imunoenzymatické techniky MeSH
- lidé MeSH
- oxidace-redukce MeSH
- poškození DNA MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Intracellular production of reactive oxygen species (ROS) plays an important role in the control of cell physiology. For the assessment of intracellular ROS production, a plethora of fluorescent probes is commonly used. Interestingly, chemical structures of these probes imply they could be substrates of plasma membrane efflux pumps, called ABC transporters. This study tested whether the determination of intracellular ROS production and mitochondrial membrane potential by selected fluorescent probes is modulated by the expression and activity of ABC transporters. The sub-clones of the HL-60 cell line over-expressing MDR1, MRP1 and BCRP transporters were employed. ROS production measured by luminol- and L-012-enhaced chemiluminescence and cytochrome c reduction assay showed similar levels of ROS production in all the employed cell lines. It was proved that dihydrorhodamine 123, dihexiloxocarbocyanine iodide, hydroethidine, tetrachloro-tetraethylbenzimidazolocarbo-cyanine iodide and tetramethylrhodamine ethyl ester perchlorate are substrates for MDR1; dichlorodihydrofluoresceine, hydroethidine and tetramethylrhodamine ethyl ester perchlorate are substrates for MRP1; dichlorodihydrofluoresceine, dihydrorhodamine 123, hydroethidine and tetrachloro-tetraethylbenzimidazolocarbo-cyanine iodide are substrates for BCRP. Thus, the determination of intracellular ROS and mitochondrial potential by the selected probes is significantly altered by ABC transporter activities. The activity of these transporters must be considered when employing fluorescent probes for the assessment of ROS production or mitochondrial membrane potential.
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- ABC transportéry genetika metabolismus MeSH
- fluorescenční barviva analýza MeSH
- HL-60 buňky MeSH
- intracelulární prostor metabolismus MeSH
- lidé MeSH
- membránový potenciál mitochondrií MeSH
- mitochondrie metabolismus MeSH
- nádorové buněčné linie MeSH
- oxidancia metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- reaktivní formy kyslíku analýza metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The catalytic role of iron in the Haber-Weiss chemistry, which results in propagation of damaging reactive oxygen species (ROS), is well established. In this review, we attempt to summarize the recent evidence showing the reverse: That reactive oxygen and nitrogen species can significantly affect iron metabolism. Their interaction with iron-regulatory proteins (IRPs) seems to be one of the essential mechanisms of influencing iron homeostasis. Iron depletion is known to provoke normal iron uptake via IRPs, superoxide and hydrogen peroxide are supposed to cause unnecessary iron uptake by similar mechanism. Furthermore, ROS are able to release iron from iron-containing molecules. On the contrary, nitric oxide (NO) appears to be involved in cellular defense against the iron-mediated ROS generation probably mainly by inducing iron removal from cells. In addition, NO may attenuate the effect of superoxide by mutual reaction, although the reaction product-peroxynitrite-is capable to produce highly reactive hydroxyl radicals.
- MeSH
- aktivace neutrofilů účinky léků MeSH
- antagonisté histaminu H1 farmakologie MeSH
- benzothiepiny farmakologie MeSH
- finanční podpora výzkumu jako téma MeSH
- histamin farmakologie MeSH
- lidé MeSH
- luminol analogy a deriváty farmakologie MeSH
- neutrofily metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Check Tag
- lidé MeSH
