[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.

[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.