[The role of myeloperoxidase, paraoxonase and nitric oxide system in blood and pericardial fluid in patients with IHD who underwent direct myocardial revascularization.]

76 patients with coronary artery disease who underwent aortocoronary bypass surgery were examined to study the role of paraoxonase, myeloperoxidase, arginase, asymmetric dimethylarginine and nitric oxide in the mechanisms of the pathogenesis of post-pericardiotomy syndrome (PPCS). Patients were divided into two groups: the 1st - patients with coronary artery disease, who did not have PPCS as a result of clinical studies; the 2nd- patients with ischemic heart disease (IHD who were diagnosed with PPCS. The results showed that the postoperative period after coronary artery bypass grafting is associated with inhibition of paraoxonase, activation of myeloperoxidase, increased activity of arginase, nitrite/nitrate level and asymmetric dimethylarginine, and may be accompanied by the development of endothelial dysfunction and increased systemic inflammatory response. In the present work, inverse correlation relationships between the arylesterase activity of paraoxonase and myeloperoxidase activity in plasma, as well as between the aryl esterase activity of paraoxonase in the blood plasma and the activity of arginase in erythrocytes of the patients of the two studied groups were established. tests were developed on basis of ratio of the enzymes activities to predict the development of post-pericardicotomy syndrome.

SkQ1 Controls CASP3 Gene Expression and Caspase-3-Like Activity in the Brain of Rats under Oxidative Stress.

Here, we studied the effect of the mitochondria-targeted antioxidant SkQ1 (plastoquinone cationic derivative) on the CASP3 gene expression and caspase-3 activity in rat cerebral cortex and brain mitochondria under normal conditions and in oxidative stress induced by hyperbaric oxygenation (HBO). Under physiological conditions, SkQ1 administration (50 nmol/kg, 5 days) did not affect the CASP3 gene expression and caspase-3-like activity in the cortical cells, as well as caspase-3-like activity in brain mitochondria, but caused a moderate decrease in the content of primary products of lipid peroxidation (LPO) and an increase in the reduced glutathione (GSH) level. HBO-induced oxidative stress (0.5 MPa, 90 min) was accompanied by significant upregulation of CASP3 mRNA and caspase-3-like activity in the cerebral cortex, activation of the mitochondrial enzyme with simultaneous decrease in the GSH content, increase in the glutathione reductase activity, and stimulation of LPO. Administration of SkQ1 before the HBO session maintained the basal levels of the CASP3 gene expression and enzyme activity in the cerebral cortex cells and led to the normalization of caspase-3-like activity and redox parameters in brain mitochondria. We hypothesize that SkQ1 protects brain cells from the HBO-induced oxidative stress due to its antioxidant activity and stimulation of antiapoptotic mechanisms.

SkQ1 Regulates Expression of Nrf2, ARE-Controlled Genes Encoding Antioxidant Enzymes, and Their Activity in Cerebral Cortex under Oxidative Stress.

The administration of SkQ1 to rats at the dose of 50 nmol/kg for five days significantly increased the mRNA levels of transcription factor Nrf2 and of Nrf2-controlled genes encoding antioxidant enzymes SOD1, SOD2, CAT, and GPx4, whereas changes in the level of mRNA of SOD3 in the cerebral cortex of the rat brain were not significant. This was accompanied by activation of antioxidant enzymes (SOD, CAT, GPx, and GST) and increase in reduced glutathione concentration. Under oxidative stress induced by hyperoxia (0.5 MPa for 90 min), the mRNA level of transcription factor Nrf2 decreased, whereas changes in the transcriptional activity of Nrf2-induced genes (SOD1-3, CAT, GPx4) encoding antioxidant enzymes in the cortex of the rat brain hemispheres were insignificant. Under conditions of hyperoxia, lipid peroxidation intensity was increased, CAT was inhibited, and GST activity was moderately increased, whereas SOD and GPx activities in the rat brain cerebral cortex remained at the stationary level. Pretreatment with SkQ1 before the exposure to hyperbaric oxygenation led to an increase in mRNA level of transcription factor Nrf2 and of Nrf2-induced genes (SOD1-2, CAT, and GPx4) encoding antioxidant enzymes, whereas SOD3 expression in the cerebral cortex of the rat brain under oxidative stress was not changed. Concurrently, we observed an increase in activities of these antioxidant enzymes (SOD, CAT, GPx, and GST) and in level of reduced glutathione. We hypothesize that the protective effect of SkQ1 under hyperoxia-induced oxidative stress could be realized via direct antioxidant activity and through stimulation of the signaling defense system Keap1/Nrf2/ARE.

[Concentration of proinflammatory cytokines, peroxiredoxin-1 and glutathione peroxidase activity in the blood plasma of patients with coronary artery disease undergoing coronary artery bypass grafting].

76 patients with coronary heart disease (who had undergone coronary artery bypass grafting) were examined to investigate the role of pro-inflammatory cytokines and enzymes involved in redox regulation, in the mechanisms of development of systemic inflammatory response syndrome. Patients were divided into 2 groups: 1st - patients with coronary heart disease, who as a result of clinical trials has not been set postpericardiotomy syndrome; 2nd - patients with coronary heart disease who have been diagnosed postpericardiotomy syndrome. The blood plasma of both groups indicated intensification of production of interleukin-6, intrleukin-8, as well as - an imbalance in the peroxiredoxin-1 and glutathione peroxidase. These changes by patients with postpericardiotomy syndrome are observed at the earliest time and differed depth of expression. The results of this work confirm the high potential of the investigated indicators for prevention and monitoring postpericardiotomy syndrome development.

Analysis of the Relationship between Antioxidant Enzyme Gene Polymorphisms and Their Activity in Post-Traumatic Gonarthrosis.

Analysis of polymorphisms of genes encoding antioxidant enzymes SOD1 (G7958A), SOD2 (T58C), CAT (C-262T), and GSTP1 (Ile105Val) in 93 patients with post-traumatic gonarthrosis showed that GSTP1 Ile105Val polymorphism is often associated with heterozygous mutation in catalase gene CAT C-262T. In gonarthrosis, catalase activity in peripheral blood mononuclear cells in patients with CT genotype of the C-262T locus of CAT gene more than 2-fold surpassed that in CC genotype and more than 50% surpassed the normal. Changes in the balance of activity of antioxidant enzymes can affect viability of mononuclear cells.

[PROINFLAMMATORY CYTOKINE GENE POLYMORPHISMS AND THE PLASMA AND SYNOVIAL FLUID LEVELS OF CYTOKINES IN PATIENTS WITH POST-TRAUMATIC KNEE OSTEOARTHRITIS].

Post-traumatic knee osteoarthritis patients (n=117) and healthy people (n=94) were investigated to determine the genotypic and allelic frequency distribution of polymorphic loci Т-31С, С+3953Т IL-1ß and G-308A TNF-α. The plasma and synovial fluid levels of proinflammatory cytokines IL-1ß and TNF-α were measured in 31 patients. The research demonstrated that the blood and synovial fluid levels of IL-1ß but not TNF-α were increased in patients with post-traumatic knee osteoarthritis. Also, the linkage between TNF-α level and polymorphic locus G-308A TNF-α was shown: the presence of allele -308А was associated with decreased TNF-α level. We demonstrated that polymorphic loci Т-31С, С+3953Т IL-1ß and G-308A TNF-α do not predict the higher risk of post-traumatic knee osteoarthritis development in Russian population of Rostov-on-Don region.

Influence of SkQ1 on Expression of Nrf2 Gene, ARE-Controlled Genes of Antioxidant Enzymes and Their Activity in Rat Blood Leukocytes under Oxidative Stress.

The study demonstrated that oxidative stress induced by hyperoxia (0.5 MPa for 90 min) resulted in reduction of mRNA levels of transcription factor Nrf2 and Nrf2-induced genes encoding antioxidant enzymes (SOD1, CAT, GPx4) in peripheral blood leukocytes of rats. The changes in gene expression profiles under hyperoxia were accompanied by disbalance of activity of antioxidant enzymes in the leukocytes, namely activation of superoxide dismutase and inhibition of catalase, glutathione peroxidase, and glutathione-S-transferase. Pretreatment of rats with SkQ1 (50 nmol/kg for five days) significantly increased mRNA levels of transcription factor Nrf2 and Nrf2-induced genes encoding antioxidant enzymes SOD2 and GPx4 and normalized the transcriptional activity of the SOD1 and CAT genes in the leukocytes in hyperoxia-induced oxidative stress. At the same time, the activity of catalase and glutathione peroxidase was increased, and the activity of superoxide dismutase and glutathione-S-transferase returned to the control level. It is hypothesized that protective effect of SkQ1 in hyperoxia-induced oxidative stress can be realized via a direct antioxidant property and the stimulation of the Keap1/Nrf2 redox-sensitive signaling system.

Influence of SkQ1 on Expression of Nrf2 Transcription Factor Gene, ARE-Controlled Genes of Antioxidant Enzymes and Their Activity in Rat Blood Leukocytes.

This study demonstrated that pretreatment of rats with mitochondria-targeted antioxidant SkQ1 (50 nmol/kg during 5 days) significantly increased the mRNA levels of Nrf2 transcription factor and Nrf2-induced genes encoding antioxidant enzymes SOD1, SOD2, CAT, and GPx4 in rat peripheral blood leukocytes. The increase in expression of these genes with SkQ1 addition was accompanied by increased activities of catalase, glutathione peroxidase, and glutathione-S-transferase in leukocytes. These results indicate that antioxidant properties of SkQ1 might be realized via induction of expression of the genes regulating activity of antioxidant system elements.

[FEATURES OF OXIDATIVE STRESS IN THE BLOOD AND THE SYNOVIAL FLUID ASSOCIATED WITH KNEE OSTEOARTHRITIS].

The features of regulation of free radical oxidation in the blood and the synovial fluid have been studied in patients with knee osteoarthritis. The data were obtained from 46 patients with primary knee osteoarthritis (II-III Kellgren-Lawrence grade, aged 63.26 ± 9.18) and 27 healthy controls. It was defined that the blood plasma was characterized by increased superoxide-eliminating activity and a tendency to the increasing of nitrite/nitrate concentration (nitrosative stress biomarkers). The erythrocytes were measured to have the increased concentration of malondialdehyde (secondary product of lipid peroxidation), activation of superoxide dismutase, gIutathione-S-transferase and reduced glutathione peroxidase activity and glutathione content. The peripheral blood mononuclear fraction of patients with osteoarthritis was characterized by significant activation of superoxide dismutase and glutathione-S- transferase, moderate catalase activation, non-significant glutathione peroxidase activity alterations and increased activity of xanthine oxidoreductase and myeloperoxidase. Finally redox-balance disturbance in the mononuclear cells leaded to oxidative stress development, which promoted lymphocytes apoptosis.

[Chemiluminescence analysis of oil oxidizing bacteria Actinetobacter calcoaceticus extracts: effects of the extracts on pSoxS-lux biosensor].

A comparative H2O2-luminol- and Fe(II)-induced chemiluminescence analysis of extracts of two strains of marine oil oxidizing bacteria Actinetobacter calcoaceticus cultivated either in the presence or absence of oil was carried out. Effects of these extracts on E. coli MG1655 biosensor (pSoxS-lux) were studied. Activation of H2O2-induced chemiluminescence in the presence of oil was observed. This suggests activation of free radical lipid peroxidation. Aqueous extracts of microorganisms cultivated in the presence of oil were shown to activate reactive oxygen species production (ROS) in Fe(II)-induced chemiluminescence reaction mixture. Acetone-ethanol extracts induced antioxidative systems of both strains. Chemiluminescence analysis in a biological system carried utilizing E. coli MG1655 (pSoxS-lux) revealed that aqueous extracts of the strains cultivated in the absence of oil contained potential antioxidants.

[Permeability of rat neurohypophysial blood vessels for neurophysins and ferritin in acute hyperoxia].

The time course of the release of vasopressin-binding (nicotine-stimulated) and oxytocin-binding (estrogen-stimulated) neurophysins (NPs) into the rat pituitary and blood serum has been studied during the convulsive phase of hyperbaric oxygenation (HBO) and the postconvulsive period (PCP). The ultrastructure of the posterior pituitary (neurohypophysis) and the state of the blood-pituitary barrier in the caudal region of the gland have been studied with the use of ferritin as an exogenous marker of vascular permeability.

[Mechanism of enzymatic dismutation of superoxide anion-radicals]. / K voprosu o mekhanizme fermentativnoi dismutatsii superoksidnykh anion-radikalov.

The mechanism of interaction of the superoxide radical O2-. with lysine was studied by the methods of polarography and ab initio quantum chemical calculations. It was shown that O2-. interacts with lysine to form a thermodynamically stable complex with proton transfer and formation of the HO2. radical.

[Emoxipin correction of disorders of lipid peroxidation as affected by a slight excess of oxygen pressure]. / Korrektsiia émoksipinom narushenii perekisnogo okisleniia lipidov pri deistvii nizkogo izbytochnogo davleniia kisloroda.

The role of the emoxipin (Em.) (2-ethyl-6-methyl-3-oxipyridine) in the correction of the free radical oxidation and allied processes in lung tissues and blood plasma under high-pressure oxygen-prolonged action has been investigated. The studied oxygen exposure (0.3 MPa, 5h) causes the lung stage of oxygen intoxication. It is confirmed by exterior morphological assessment of the lung. The lipid peroxidation increase in lung tissue and blood plasma as well as erythrocyte membranes destabilization result from oxygen exposure. Lipid peroxidation intensity was estimated by determining of content of lipid peroxidation molecular products such as diene conjugates and Shiffs' bases. Erythrocyte membranes stability was evaluated with hemoglobin yield, total iron level and total peroxidase activity in blood plasma. Emoxipin was injected intraperitoneally in a dose 150 mg per 1 kg rats' weight just before the oxygen exposure. Emoxipin is found to improve physiological state of animals and to increase their survival; it normalizes morphology of the lungs and their state; stabilizes erythrocyte membranes injured under oxygen exposure; decreases intensity of lipid peroxidation processes in the lungs and in blood plasma which was previously increased under hyperoxia.

[Micro-determination of the intensity of luminol-dependent chemiluminescence of plasma]. / Mikroopredelenie intensivnosti liuminolzavisimoi khemiliuminestsentsii plazmy.

The authors attempted to modify the macro-method for assessment of the intensity of luminol-dependent chemiluminescence by using small volumes of capillary blood, diluted 100-fold. They have demonstrated the compatibility of two methods for blood collection, from the vein and from the finger, on the basis of the rapid test of oxygen intoxication severity and individual sensitivity of the body to hyperoxia in vitro. Use of microvolumes of the sample for analysis will facilitate the clinical application of the test for the selection of the optimal HBO schemes.

[Biochemical indicators of oxygen poisoning]. / Biokhimicheskie pokazaniia kislorodnoi intoksikatsii.

Content of extra erythrocyte hemoglobin (EEH), total peroxidase activity (TPA), tseruloplasmin oxidase activity (TOA) and chemiluminescence intensity have been investigated in plasma. The dose-dependent changes of EEN, TPA, TOA are shown in experiments on the animals under hyperbaric oxygen (HBO) pressure (0.2, 0.3, 0.5, 0.7 MPa from 30 min. to 120 min.) and EEH, TPA--under hyperbaric air (1.1 MPa; 4 hours). All these parameters have been studied in patients treated with HBO for the assessment of HBO efficacy in the clinical investigations. These biochemical parameters may be used as informative tests of the functional state of the organism under HBO and hyperbaric air.

[Iron-containing proteins in the plasma and serum of the blood in patients during hyperbaric oxygenation therapy]. / Zhelezosoderzhashchie belki v plazme i syvorotke krovi bol'nykh pri giperbarooksigenoterapii.

Extra-erythrocyte hemoglobin (EEH) level and total peroxidase activity (TPA) have been analysed in the blood serum and plasma of 44 patients following hyperbaric oxygenation (HBO). The levels of the parameters tested decreased after 3 HBO procedures and remained low to the end of the treatment period in the first group of patients. In the second group of patients, on the contrary, EEH and TPA levels increased after 3 HBO procedures and remained high to the end of the treatment period. In both groups of patients EEH changes correlated with TPA alterations. Possible EEH and TPA determination for the estimation and enhancement of HBO treatment efficacy is discussed.

[Use of blood biochemical parameters for evaluating the clinical effectiveness of hyperbaric oxygenation therapy]. / Ispol'zovanie nekotorykh biokhimicheskikh pokazatelei krovi dlia otsenki éffektivnosti giperbarooksigenoterapii v klinike.

Changes in the total peroxidase activity (TPA) and extraerythrocyte hemoglobin (EEH) content have been studied in the blood plasma and serum of patients treated with hyperbaric oxygenation (HBO). TPA and EEH content after the 3rd HBO session increased by 38% and 257%, respectively, in the plasma and by 56% and 74%, respectively, in the serum. By the end of HBO therapy course, after the 8th session, plasma level of the parameters under study normalized, while their serum level was higher than baseline. Possible use of the parameters under study for the assessment of HBO efficacy is discussed.

[Changes in the concentration of metalloproteins in the blood plasma in hypoxia and hyperbaric oxygenation]. / Izmenenie kontsentratsii metallosoderzhashchikh belkov v plazme krovi pri gipoksii i giperbaricheskoi oksigenatsii.

Dynamics of hemoglobin, ceruloplasmin concentration, the changes of chemiluminescence in blood plasma and kinetics of rat erythrocyte heat denaturation during consequent exposition of high altitude hypoxia and hyperbaric oxygenation have been studied. Severe hypoxia causes the decrease of extraerythrocyte hemoglobin and oxidase activity of ceruloplasmin. Reoxygenation results in significant increase of blood plasma chemiluminescence with simultaneous increase of extraerythrocyte hemoglobin level and with modification of surface structure of the erythrocyte membranes. Possible pathways of activation of oxygen-dependent of free-radical processes during reoxygenation are discussed.