[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).

[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.

[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 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.