[Clinical and biochemical heterogeneity of Parkinson's disease]. / Klinicheskaya i biokhimicheskaya geterogennost' bolezni Parkinsona.

OBJECTIVE: To study correlations between oxidative stress (OS) and clinical changes in patients with neurodegenerative Parkinson's and to identify clinical/biochemical subtypes of the disease. MATERIAL AND METHODS: One hundred and nine people were studied, including 91 patients with neurodegenerative Parkinson's (72 patients with Parkinson's disease (PD); 10 with multiple system atrophy (MSA); 9 with corticobasal degeneration (CBD), average age 61.1±7.2 years), and 18 clinically healthy people (average age 55.1±9.2). OS indexes were detected for scoring of redox state in peripheral blood of patients with PD and healthy people (control group). Detection of biochemical indexes was performed in erythrocytes and mononuclear fraction and blood. The activity of glutathione reductase (GR), myeloperoxidase (MPO) and content of reduced glutathione (GSH) was estimated. RESULTS AND CONCLUSIONS: OS is a universal mechanism and is observed in many neurodegenerative diseases. However it is possible to identify quite typical changes of redox state with group selection and their correlations with definite subtypes and PD progress, it gives opportunity, in particular, to make the differential diagnosis with atypical Parkinsonism.

[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.

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.

Effect of plastoquinone derivative 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) on contents of steroid hormones and NO level in rats.

Introduction of the plastoquinone derivative 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) into male Wistar rats once a day for two weeks in doses of 25 and 250 nmol/kg led to elevation of 17ß-estradiol level in blood serum by 33 and 41%, respectively. At the same time, nitrate and nitrite contents in the rat blood serum increased by 49 and 34%, respectively. ESR spectroscopy with diethyldithiocarbamateiron complex as a spin trap showed more than twofold increase in NO production in lungs, but not in blood, liver, and intestines, following the SkQ1 daily introduction at a dose of 25 nmol/kg.

Effect of artrofoon and SCENAR therapy on parameters of LPO and antioxidant system of the blood in patients with peritonitis in postoperative period.

Administration of artrofoon in combination with SCENAR therapy to patients with localized suppurative peritonitis in the postoperative period considerably reduced plasma MDA level, stabilized ceruloplasmin activity, and increased catalase activity in erythrocytes compared to the corresponding parameters in patients receiving standard treatment in combination with SCENAR therapy.

Structural and functional characteristics of erythrocyte membranes and their correction with perftoran.

We studied the effect of single intravenous injection of perftoran on the intensity of the initial stages of lipid peroxidation and structural and functional characteristics of erythrocyte membranes (cell model). Perftoran slightly activated the initial stages of lipid peroxidation and optimized structural and functional characteristics of erythrocyte membranes.

Regulation of free radical processes by delta-sleep inducing peptide in rat tissues under cold stress.

An intraperitoneal injection of an exogenous delta-sleep inducing peptide (DSIP) at a dose of 12 microg/100 g body weight shifted the prooxidant-antioxidant balance of free radical process (FRP) in tissues and erythrocytes of rats: the activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and the concentrations of antioxidants (reduced glutathione in particular) increased. The DSIP stimulated the myeloperoxidase activity in blood neutrophils and had no effect on the activity of xanthine oxidase, a prooxidant enzyme, in the brain and liver. Cold stress displaced the prooxidant-antioxidant balance by increasing the xanthine oxidase activity in tissues and decreasing the myeloperoxidase activity in blood neutrophils; it also inhibited the enzyme antioxidant activities in tissues and erythrocytes that was neutralized by an increased ceruloplasmin activity in blood plasma and by an elevated level of antioxidants in rat blood and tissues. Preliminary administration of DSIP to animals exposed to cold stress restored the prooxidant-antioxidant balance: it normalized the myeloperoxidase activity in blood neutrophils, decreased the xanthine oxidase activity, and increased the activity of antioxidant enzymes in tissues and erythrocytes restoring the antioxidant level. The molecular regulation mechanism of free radical processes by DSIP in tissues under stressful conditions is discussed.

The effects of delta sleep-inducing peptide on the intensity of lipid peroxidation and xanthine oxidase activity in rat tissues during cold stress.

Exogenous delta sleep-inducing peptide given i.p. to intact rats at a dose of 12 microg/100 g decreased the levels of diene conjugates and Schiff bases in liver and brain tissues and had no effect on xanthine oxidase activity in these tissues. Cold stress was accompanied by increases in xanthine oxidase activity in rat liver and brain, with a consequent accumulation of diene conjugates and Schiff bases, as compared with intact animals. Preliminary administration of delta sleep-inducing peptide before three days of cold stress led to decreases in xanthine oxidase activity and lipid peroxidation products in the liver and brain, as compared with values in stressed rats. The protective effect of delta sleep-inducing peptide in stress is discussed.