Features of oxidative stress in alcoholism.

The review considers molecular mechanisms underlying formation and development of oxidative stress (OS) in patients with alcohol dependence. The major attention is paid to the effects of ethanol and its metabolite acetaldehyde associated with additional sources of generation of reactive oxygen species (ROS) in response to exogenous ethanol. The own results of studies of the in vitro effect of ethanol and acetaldehyde on the concentration of peripheral OS markers - products of oxidative modification of proteins (protein carbonyls), lipids (lipid peroxidation products), DNA (8-hydroxy-2-deoxyguanosine, 8-OHdG) in blood plasma are presented. The changes in these parameters and the activity of antioxidant enzymes (SOD, catalase) in patients with alcohol dependence were analyzed. Own and literature data indicate that at a certain stage of the disease OS can play a protective rather than pathogenic role in the body.

Cytokine Production in Whole Blood Cells Culture of Patients with Alcohol Dependence and Autologous Plasma Oxidative Stress Markers.

We studied spontaneous production of a spectrum of proinflammatory cytokines by cultured whole blood cells from men with alcohol dependence at the stage of withdrawal syndrome and oxidative stress markers (carbonylated proteins and TBA-reactive substances) in the plasma of these blood samples. Enhanced production of cytokines by blood cells and increased concentrations of oxidative stress markers in the autologous plasma were revealed in comparison with the corresponding parameters in the control (blood from healthy men). Direct correlations were found between the levels of spontaneous cytokine production by blood cells from subjects with alcohol dependence and the concentration of oxidized proteins and lipids in autologous plasma.

[Hormones of stress-response system in alcohol dependence: the ability to predict duration of remission]. / Gormony stress-realizuyushchei sistemy pri alkogol'noi zavisimosti: vozmozhnost' prognozirovaniya dlitel'nosti remissii.

OBJECTIVE: To determine the spectrum of hormones of the stress-realizing system in the time course of therapy of withdrawal syndrome and post-withdrawal state and analyze their possible relationships with the duration of therapeutic remission in patients with alcohol dependence. MATERIAL AND METHODS: The examination included 74 men admitted in the clinic at Mental Health Research Institute NRMC diagnosed as having «Mental and behavioral disorders due to use of alcohol¼ (dependence syndrome F10.21 and withdrawal state - F10.30) according to ICD-10. The control group included 35 men matched in age with patients. Concentration of cortisol, testosterone, and thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) were determined by immunoenzyme method (IEM), in patients - at two points: point 1 - by day 3-5 of the admission in the clinic in the withdrawal syndrome state after alcohol detoxification; point 2 - by day 15-17 of the anti-alcohol therapy. RESULTS: In the general group of patients with alcohol dependence the elevation of the level of cortisol in comparison with control was established (pc<0,0001 at both points) and increase of concentration at point 2 (p=0,0253 to point 1). Concentration of testosterone at point 1 exceeded the level of control (pc=0,0203), at point 2 decreased up to control values and in relation to point 1 (p=0,0004). In relation to control the level of TSH in patients was decreased at point 1 (pc=0,0077); the concentration of fT3 and fT4 was reliably decreased at both points; concentration of fT4 decreased further in the process of the therapy of the post-withdrawal state (p=0,0003 to point 1). According to the duration of the last therapeutic remission, two groups of patients were formed: those with unstable remission (up to 6 months) and with the formed stable remission (1 year or more). A comparative analysis of the concentration of cortisol and testosterone in blood serum taken in patients at point 1 revealed a significant excess of testosterone in the group with unstable remission, both in relation to the control (pc=0,0239) and to the indicator in the group of patients with stable remission (p=0,0159). CONCLUSION: Dysfunctions in the spectrum of stress-realizing hormones in patients with alcohol dependence in the time course of the therapy for withdrawal syndrome and post-withdrawal state were revealed, the main of which are high level of cortisol, testosterone, reduction of secretion of free thyroxine and free triiodothyronine. Patients with unstable therapeutic remission are characterized by a high concentration of testosterone after alcohol detoxification, which allows us to consider testosterone as a biological criterion that can increase the accuracy of prediction of the duration of remission after anti-alcohol therapy.

[Protective action of carnosine and organic lithium salts in case of ethanol-induced oxidative damage of proteins and lipids of blood plasma in healthy persons and alcoholic patients]. / Protektornoe deistvie karnozina i organicheskikh solei litiia pri étanol-indutsirovannom okislitel'nom povrezhdenii belkov i lipidov plazmy krovi u zdorovykh lits i bol'nykh alkogolizmom.

Organic lithium salts containing anionic components (succinate, fumarate, pyruvate and antioxidant ascorbate) were tested for protection of blood plasma proteins and lipids against ethanol-induced oxidation in vitro. We used normothymic lithium carbonate and well-known antioxidant dipeptide carnosine (b-alanyl-L-histidine) as the reference drugs. The oxidized proteins and lipids were determined by the level of carbonylated proteins (CP) and TBA-reactive products (TBA-RP), respectively. In alcoholic patients the level of oxidized proteins and lipids was higher than in healthy persons. Incubation of blood with ethanol resulted in an increase in oxidized proteins and lipids in blood plasma of healthy persons but had no influence on the level of CP and TBA-RP in blood plasma of alcoholic patients. Lithium carbonate, lithium ascorbate, and lithium succinate exhibited protective action against ethanol-induced oxidation of biomolecules of blood plasma of healthy people. These effects were comparable with carnosine action. The studied compounds had no effect on the level of CP and TBA-RP of blood plasma of alcoholic patients.

[Indices of the antioxidant system and dopamine in blood plasma in the dynamics of microwave resonance therapy in patients with alcoholism]. / Pokazateli antioksidantnoi sistemy i dofamina plazmy krovi v dinamike mikrovolnovoi rezonansnoi terapii u bol'nykh alkogolizmom.

AIM: To study effects of microwave resonance therapy (MWRT) on the level of dopamine and some indices of the antioxidant system of blood plasma in patients with alcohol dependence. MATERIAL AND METHODS: Dopamine, reduced glutathione, activities of catalase and superoxidismutase (SOD) were measured in blood plasma of alcoholic patients (50 men) before and after therapy. Plasma of 25 physically and mentally healthy men matched for age was used as control. RESULTS: In alcoholic patients in withdrawal state, the significant increase in dopamine (p=0.03), activity of catalase and SOD (p<0.05) as well as a decrease in reduced glutathione (p<0.01) in blood plasma in comparison with controls were found. The level of dopamine decreased significantly as after conventional therapy, as well after the therapy with addition of MWRT. After MWRT, the level of glutathione in blood plasma increased significantly and activities of catalase and SOD decreased practically up to the control level while after conventional therapy (without MWRT), the indices of the antioxidant system did not change significantly. CONCLUSION: The inclusion of MWRT in complex treatment of patients with alcoholism contributes to the normalization of the activity of catalase and SOD and increases the level of reduced glutathione, but has no significant effect on blood plasma dopamine level.

Molecular and Cellular Bases of Iron Metabolism in Humans.

Iron is a microelement with the most completely studied biological functions. Its wide dissemination in nature and involvement in key metabolic pathways determine the great importance of this metal for uni- and multicellular organisms. The biological role of iron is characterized by its indispensability in cell respiration and various biochemical processes providing normal functioning of cells and organs of the human body. Iron also plays an important role in the generation of free radicals, which under different conditions can be useful or damaging to biomolecules and cells. In the literature, there are many reviews devoted to iron metabolism and its regulation in pro- and eukaryotes. Significant progress has been achieved recently in understanding molecular bases of iron metabolism. The purpose of this review is to systematize available data on mechanisms of iron assimilation, distribution, and elimination from the human body, as well as on its biological importance and on the major iron-containing proteins. The review summarizes recent ideas about iron metabolism. Special attention is paid to mechanisms of iron absorption in the small intestine and to interrelationships of cellular and extracellular pools of this metal in the human body.

Use of Carnosine for Oxidative Stress Reduction in Different Pathologies.

The main properties and biological effects of the antioxidant carnosine, the natural dipeptide ß-alanyl-L-histidine, are considered. Data on the effective use of carnosine in different pathologies are presented. Special attention is paid to issues of use of carnosine in neurologic and mental diseases, in alcoholism as well as in physiological states accompanied by activation of free-radical processes and formation of oxidative stress.

In vitro effects of ethanol, acetaldehyde and fatty acid ethyl esters on human erythrocytes.

In vitro experiments were performed to determine if ethanol was metabolized by human erythrocytes and to investigate if ethanol or its metabolites, acetaldehyde and fatty acid ethyl esters, affected erythrocyte morphology and stability. No detectable metabolism of ethanol was found in erythrocytes, although ethanol itself caused an elevated rate of spontaneous haemolysis in erythrocyte preparations. Physiologically attainable levels of ethanol were found to stabilize erythrocytes against haemolysis induced by sodium hypochlorite, and the presence of ethanol caused a decrease in erythrocyte reactive oxygen species levels, although the mechanism for such a process is unknown. Both physiologically attainable and higher levels of acetaldehyde had no effects on erythrocyte morphology and stability even after a 16 h exposure. Fatty acid ethyl esters caused structural changes and instability in erythrocytes in vitro, but whether such changes occur in vivo has not been established. The results of these studies suggest that the deleterious effects of ethanol consumption on erythrocytes in vivo may be, at least in part, the result of direct effects of unmetabolized ethanol on erythrocyte components.

Does ethanol metabolism affect erythrocyte hemolysis?

The effects of ethanol and acetaldehyde on the hemolytic stability of rabbit erythrocytes have been compared. Incubation of normal erythrocytes with ethanol facilitated both acidic and oxidative hemolysis and increased the percentages of cells that were hemolyzed at maximal rate. Acetaldehyde exerted a similar destabilizing effect on erythrocytes only in the case of oxidative hemolysis. The destabilizing effect of ethanol was observed in catalase-inactivated erythrocytes under acidic, but not oxidative, hemolysis conditions. It is concluded that the destabilizing effect of unmetabolized ethanol occurs under conditions of acidic hemolysis, whereas the destabilizing effect of the oxidation of ethanol to acetaldehyde takes place only under the conditions of oxidative hemolysis.

Effects of carnosine and related compounds on the stability and morphology of erythrocytes from alcoholics.

The effects of carnosine and related compounds on erythrocytes from alcoholics were studied. In their presence, erythrocytes showed an increased ability to resist haemolysis and showed a more normal morphology, with carnosine and N-acetyl-carnosine being the most effective compounds. These beneficial properties of the dipeptides do not appear to be directly related to their antioxidant or buffering properties.

Effect of calmodulin inhibitors on rat and guinea pig myocardial contractility.

The effects of phenothiazine drugs with different affinities for calmodulin (trifluoperazine, frenolone, majeptile and aminazine) on the contractility of rat and guinea pig papillary muscles were studied. The phenothiazine-induced changes in the contraction-relaxation parameters were shown to correlate with the degree of calmodulin inhibition. These parameters are relaxation-onset index, relaxation index and terminal relaxation index in rats, and relaxation index and maximal developed tension in guinea pigs. An essential role of calmodulin in myocardium relaxation in both animal species is postulated.