[MORPHOLOGICAL ALTERATIONS IN THE INTERNAL ORGANS OF RATS WITH ALLOXAN DIABETES].

The aim of our study was to assess morphological changes in internal organs in a redox-induced model of alloxan diabetes in rats.According to the results of the study, the blood glucose level in rats began to increase 24 hours after the of alloxan administration, reached the maximum level on the 15th day of observation, and decreased on the 25-35 day, to the control level. In parallel with the increase in blood glucose level, an increase in the malondialdehyde (MDA) content in the blood serum was observed.Severe hyperemia, edema, and focal fibrotic changes were revealed morphologically in the kidneys, liver and myocardium. The degree of morphological changes was increased (lymphocytic-cell infiltration, degenerative changes (dystrophy), small necrotic areas) with an increase in the level of glucose and MDA in the blood. It can be assumed that the damage to the tissues of the kidneys, heart, liver and blood vessels in diabetes is largely due to the intensification of oxidative stress in the body.

CHANGES OF ENDOTHELIN-1 CONTENT AND BLOOD RHEOLOGICAL PROPERTIES IN CRUSH SYNDROME.

This study describes hematocrit values and quantitative changes in plasma endothelin-1 (ET-1) levels according to the severity of crush syndrome (CS) compression and decompression periods. The experiments were carried out on 50 randomly selected 200-250 gr mass Wistar rats with the use of the standard crush syndrome modeling method. The plasma level of ET-1 was determined by the immuneenzyme method with the use of ELISA REDEAR URIT 660. Hematocrit was determined using the standard method and measured according to tube column divisions. Our data show that ET-1 and hematocrit values rise commensurate with an increased duration of compression, and especially decompression periods. In CS, elevation of ET-1 concentrations and hematocrit values leads to significant microcirculation disturbances in parallel with longer and more severe compression and decompression periods. Specifically, the ET-1 concentration was significantly elevated, possibly in response to activation of surface endothelial В (ET-B) receptors located in the vessel endothelium. These receptors, in turn, have a vasodilative effect due to nitrogen oxide synthesis induction and vascular smooth muscle relaxation. The rise in hematocrit values during crush syndrome is associated with plasmorrhagia induced by trauma and toxic (rhabdomyolysis) shock.

CHANGES OF LIPOPEROXIDATION AND ANTIOXIDATIVE ENZYMES DURING CRUSH-SYNDROME MODELLING.

Crush-syndrome (CS) is characterized by numerous pathological deviations due to the soft tissue damage and their further reperfusion. The aim of the study was to investigate pro- and antioxidative processes during different regimens of crush syndrome. The experiment was carried out on randomly selected 200-250gr. mass 50 laboratory rats using crush syndrome modeling classical method. Investigations were conducted at various stages of compression and decompression period. Activity of antioxidant enzymes - total ceruloplasmin, oxidized ceruloplasmin was determined in blood serum. LOO. and free oxygen species were as well determined with the use of relevant methods. According to our findings we can conclude that: - Lipoperoxidation intensity increases in compliance with crush syndrome duration; - Short-term (3-hour) compression causes enhancement of lipoperoxidation however, in further 1 hour decompression there is revealed a trend toward normalization of processes. Lipoperoxides and free oxygen species content decreases and the antioxidant enzymes activity is almost restored; - Long lasting compression (6 hours) leads to severe disorders in the body (total ceruloplasmin impaired production and after 6 hours from decompression antioxidant enzymes inactivation).

[The variants of changes in pro- and antioxidative processes in viral hepatitis and the necessity of differential approach in their antioxidative therapy].

There was investigated the changes in pro- and antioxidative processes in viral hepatitis of different etiology. It was revealed that the mechanisms mentioned above essentially differ from each other and for their treatment, accordingly, different groups of antioxidative drugs should be used. The data obtained indicates the impossibility of "universal" antioxidative therapy. The role of oxidative stress in the mechanisms of different types of hepatitis and unforeseen negative effect of antioxidative therapy requires special caution and attention in selection of mitochondrial respiratory chain stabilizing antioxidants. In hepatitis A, which is characterized by relatively less intensity of peroxidation natural antiradical remedies should be used (e.g. tocopherol). In viral hepatitis B and especially in hepatitis C, it is desirable to use the selenium-containing antioxidants. In hepatitis B, which is characterized by relatively less content of nitric oxide, it is recommended to use the stimulants of NO synthesis.

[The role of apoptosis in the development of virus hepatitis].

In present review hepatocyte apoptosis is presented as universal defensive reaction of liver, to the damages. Hepatocyte apoptosis may be caused by hepatotropic virus's direct affection, or by the immune reactions initiated by viruses. Apoptosis development caused by virus direct affection varies and contains at lest two mechanisms: production of specific proteins: B virus - X protein and C virus - core-protein; expression of the receptors leading the induction of this process on the hepatocyte membrane, for example, increasing of Fas-receptor and cell sensation to apoptosis stimulus. In apoptosis induced by immune reaction T-lymphocytes could trigger off apoptosis in two principal ways: by releasing perporines that produce holes through hepatocyte membrane and according to this process granzyms are permetted inside the cells. By destroying of caspases by proteases that initiate apoptosis cascade. In this article molecular mechanisms of the processes mentioned above are also discussed.

[Correction of oxidative stress in the rat brain cortical cellular culture with vitamines E and C].

The oxidative stress-induced alteration in concentration of oxygen, lipid and nitrogen free radicals in cultured brain cortex of the newborn albino rats and its correction with vitamins E and C was investigated. Modeling the oxidative stress was achieved with addition of H(2)O(2) into the nutrient medium. In order to prevent an oxidative stress-induced cytotoxic effect, concomitantly with H(2)O(2), vitamins E and C were added into the nutrient medium. Oxygen, lipid and nitrogen free radicals were registered by method Electron Paramagnetic Resonance (EPR) and spin-traps. The data, obtained in our study revealed decreasing of intensity of NO content and increasing of spin trapped superoxid- (O(2-)) and lipoperoxid-radicals (LOO.) in explants of brain cortex of the newborn albino rats cultured in oxidative stress conditions. These changes were attenuated following action of vitamins E and C (decreasing of intensity of EPR signals of O2- and LOO, increasing of free NO content).

Treatment of experimental autoimmune encephalomyelitis by vitamin in animal model.

Study purposed to determine the effectiveness of vitamin treatment in experimental autoimmune encephalomyelitis (EAE) animal model of multiple sclerosis (MS) by comparing several blood serum inflammatory markers, neurological deficiency and histopathological changes in untreated and treated EAE animals. Eighteen, 9-13 week old, male Wistar rats were immunised by 100 µl MOG injection. Clinical signs of EAE scored by a masked investigator. After EAE exposition all rats were divided equally as untreated control and experimental group treated by vitamins (E, C, D3). Blood was obtained from all rats before and after immunization and on 7th day of treatment. ELISA method was used to detect the serum cytokine contents of IL-6, IFN-γ, IL-10. On 10th day of disease the rats were euthanized and transverse sections of spinal cord were divided in 16 areas with score of 1 for each area showing lymphocyte infiltration or demyelination. Mann-Whitney U-test was used for determining the level of significance of differences between sample means. On 7th day of treatment neurological deficiency stayed unchanged in control and was ameliorated in experimental group (p<0.05). Significant histopathological differences were found between control and experimental groups on 10th day of EAE. Serum levels of IFN-γ, IL-6 and IL-10 were elevated after exposition of EAE against healthy rats, while on 7th day of treatment the experimental group revealed the significant differences as compared to untreated control. Positive correlation was found between IL-6 and IFN-γ serum contents and neurological deficiency on 7th day of disease (r=+0.53, p<0.02 and r=+0.49; p<0.01).

[Alterations of tissue blood supply of experimental animals at malignant tumor growth].

The aim of the research was to study tissue blood flow in the dynamics of malignant tumor growth (Ehrlich carcinoma of 80 mice, sarcoma--37-80 rats, 30 rabbit--Brown-Pirs carcinoma) in functionally different organs of experimental animals (mice, rats, rabbits): skeletal muscles, liver, ear, mammary gland and ciliary body of eye. The study was conducted using H clearance method. Deformability of erythrocytes was studied using filtration-photometry method. Blood surface tension was studied by Rebinder bubble maximal pressure method. Obtained data were analyzed by Student's t criterion. The investigation showed that intensity of local hemocirculation and erythrocytes deformability in "intact" organs and tissues of experimental animals in the dynamics of malignant tumor growth progressively decreases while, blood surface tension increases. It was revealed that paraneoplastic disorders of local hemocirculation were stereotyped, universal and common phenomenon for malignant tumor growth. It was concluded that alterations of blood rheology decreased deformability of erythrocytes and increased blood surface tension play one of the leading roles in the mechanism of paraneoplastic disorders of local hemocirculation.

[Some aspects of metabolic remodeling of myocard during chronic heart failure].

Review provides different mechanisms of "metabolic remodeling" of myocard during Chronic Heart Failure (CHF) including disorder of myocardial energy metabolism, changed activity of intracellular regulatory enzymes, metabolic activity of myocardial interstitium, different metabolic pathways leading to apoptosis of cardiomyocytes. The liquidation of results "metabolic remodeling"of myocardium prospects the new possibilities for development of pharmacological modulators of myocardial metabolic dysfunction in CHF.

[Molecular mechanisms of apoptosis].

Apoptosis is the vital issue of Biology and Medicine. Recent concept of molecular and cellular mechanisms of apoptosis--a well-controlled form of cell death was reviewed. The aim of a review was to broaden knowledge of apoptosis mechanism and to reveal molecular targets for the modulation of these processes. The data on the apoptosis was analyzed. The biological role of physiological cell death in normal state and in different human pathologies is described. The literature data showed that many molecular mechanisms of apoptosis are still unknown. Three mechanisms are actually known to be involved in the apoptotic process: a receptor-ligand mediated mechanism, a mitochondrial pathway and a mechanism in which the endoplasmic reticulum plays a central role. Morphological and biochemical definitions of poptosis are presented. An original scheme of apoptosis mechanisms is constructed. The term "mediators of poptosis" is introduced. Extra cellular and intracellular mechanisms of apoptosis are examined. The special attention is paid to mitochondrial factors of apoptosis, Ca(2+)-ions, and proteins (Bcl-2, Bax, p-53).

[The role of blood rheology and micro hemocirculation in development of generalized hypoxia in crush syndrome].

Crush syndrome (CS) is a type of traumatic pathology accompanied by intoxication of organism with a heavy and specific clinical course and high lethality. Numerous damages, the most significant of which are stress, shock, pain, violation of the neurohumoral system involving the mediators of the sympathic part of vegetative nervous system, and pathological condition in which the body as a whole (generalized hypoxia) or region of the body (tissue hypoxia) is deprived of adequate oxygen supply are common in CS. The aim of the research was to study factors, which determine tissue blood and oxygen supply and to detect the possible pathogenetic mechanisms of generalized hypoxia in decompressed tissues and organs in long CS. Systemic arterial pressure, blood supply of skeletal muscles and liver, mesenteric microcirculation, mechanical and chemical resistance of erythrocytes of rats in crash syndrome has been investigated with the use of electrotensometry, H+-clearance, telebiomicroscopy, ultrasound cytolysogram and photoelectrocolorimetry. The model of crush was created by compression of experimental animals' hip during 6 hours. The morphological study of brain tissue during different types of decompression has revealed a contraction of the vessels of the cerebral shell, hypoxia, and perivascular edema. It was stated that interrelated changes play significant role in development of generalized hypoxia of tissues; degree of disorders depend on duration of compression and decompression, reactivity of micro blood vessels; the fall of local hemocirculation in intact tissues and reduced resistance and deformability of erythrocytes takes place.

[The role of changes in tissue redox-status in mechanism of paraneoplasia].

To specify mechanisms of paraneoplastic alterations of redox-status of tissues in experimental malignant tumor growth, we investigated electronic paramagnetic centers of blood, skeletal muscle and liver with electronic paramagnetic resonance (EPR) method. We also studied the concentration and activity of antioxidant enzymes. Our experiments on adult white male rats of mixed population with sarcoma C-45 and mice with Ehrlich carcinoma have shown that malignant tumor growth leads to enhanced lipid peroxidation (LPO): production of potent LPO promoters - Fe2+, Mn+2+, NO, ubiquinone; depression of antioxidant defence - reduced production of total ceruloplasmin, elevated blood levels of oxidized ceruloplasmin and enhanced catalase activity. It is suggested that malignant tumor growth is associated with marked paraneoplastic shifts in tissue redox-potential. These alterations are involved in mechanisms of paraneoplastic changes of red cells, microhemocirculation and circulation intensity. All these interrelated processes result in generalized paraneoplastic hypoxia of the organs and tissues. Basing on our and literature data, we propose an original scheme of the mechanisms of paraneoplastic disorders of tissue redox-status, microcirculation and erythrocytes.

Changes in the prooxidant and antioxidant status of tissues during paraneoplastic processes.

Electron paramagnetic resonance was used to identify paramagnetic centers in the blood and liver of laboratory rats with S-45 sarcoma and mice with Ehrlich carcinoma. Paraneoplastic changes in prooxidant and antioxidant activity of the blood and liver tissue, mitochondrial respiration, and NO metabolism and inhibition of antioxidant processes contribute to impairment of cell membrane structures, erythrocyte hemolysis, and hypoxia. An important role of these processes in the pathogenesis of paraneoplastic anemia is confirmed by the positive effect of antioxidant and membrane-stabilizing therapy.

[Role of peroxidation processes and nitric oxide in mechanisms of paraneoplastic alterations of hemocirculation].

The present work was aimed to study mechanisms of paraneoplastic alterations of tissue redox-status, intensity of local blood flow in liver and their possible interrelations in case of malignant tumor growth. It has been investigated the electronic paramagnetic centres of blood and liver using the electronic paramagnetic resonance (EPR) method and intensity of local hemocirculation with the use of H(+) clearance polarography method. Experiments have been carried out on adult white rats of mixed population with carcinoma Walker and mice -- with carcinoma Ehrlich. It has been shown that malignant tumor growth displays conditions that lead to exaggerated lipid peroxidation (production of POL promoters -- Fe(2+), Mn(2+), NO, ubiquinone) and suppression of antioxidant protection of organism (reduction of total ceruloplasmin concentration in blood and increased concentration of oxidized ceruloplasmin). It has been suggested that in case of malignant tumor growth sharp paraneoplastic alterations of redox-status plays essential role in mechanisms of paraneoplastic disorders of tissues blood supply. All of these interrelated processes result in generalized paraneoplastic hypoxia in organs and tissues.

[Oxidative stress as common pathological phenomenon and possibilities of its correction].

It was shown that disorders of oxidative metabolism play an important role in the pathological processes which develops at subcellular level -- disorder of electron transport at ubichinon-oxidoreductase locus of respiratory chain in mitochondria. The latter could be discussed as common pathological phenomenon determining oxidative stress. It is found that altered synthesis and metabolism of nitric oxide plays an important role in the pathogenesis of oxidative stress. It has been detected the ways and mechanisms of disorders of NO synthesis and conversion. The negative role of widespread and irrational use of antioxidant therapy and "universal" antioxidant treatment was characterized.