Olga Tyulina - Academia.edu (original) (raw)

Papers by Olga Tyulina

Vascular Pharmacology

ABSTRACT

Biochemistry. Biokhimii͡a, 2000

The stability of rabbit erythrocytes to hemolysis induced by different compounds in the presence ... more The stability of rabbit erythrocytes to hemolysis induced by different compounds in the presence or absence of ethanol or acetaldehyde has been analyzed. Ethanol slightly reduced erythrocyte stability against acidic hemolysis only after long-term preincubation, but the effect of ethanol on stability to oxidative hemolysis manifested itself immediately after its addition to the cells. Ethanol decreased both stability of cells to oxidative damage and dispersion of the hemolytic curve. Comparison of the effects of ethanol and acetaldehyde showed that the destabilizing effect of ethanol might be caused by either its direct action or the effect of its metabolites formed during preincubation of ethanol with erythrocytes. Possible mechanisms of ethanol and acetaldehyde effects on erythrocyte stability are discussed.

Neurochemical Journal, 2008

Prenatal hyperhomocysteinemia induced in rats by overloading of dietary methionine (1 g/kg body m... more Prenatal hyperhomocysteinemia induced in rats by overloading of dietary methionine (1 g/kg body mass daily) results in systemic disordering in progeny related to an increase in the excitotoxic feature of NMDA-receptors in cerebellar neurons and memory suppression. Administration of carnosine (100 mg/kg body mass daily) in the diet of pregnant rats with hyperhomocysteinemia prevents both cognitive function in pups and protects cerebellar neurons from oxidative stress. The effect of carnosine is accompanied by with the restoration of superoxide dismutase in rat brain, which is decreased during hyperhomocysteinemia from 2.07 units (control) to 1.54 units.

Doklady Biochemistry and Biophysics, 2008

In this work, we demonstrate that homocysteic acid provokes oxidative stress in erythrocytes and ... more In this work, we demonstrate that homocysteic acid provokes oxidative stress in erythrocytes and decreases their hemolytic resistance, whereas the natural antioxidant carnosine [9] protects erythrocytes from its toxic effect. The discovered property can be used for development of new methods for protecting erythrocytes in hyperhomocysteinemia. Homocysteine and homocysteic acid (HCA), the product of spontaneous homocysteine oxidation, are important risk factors for neurodegenerative and cardiovascular diseases [1]. These compounds induce oxidative stress in brain neurons [2, 3] and lymphocytes [4], resulting from their toxic effect on the nervous and immune systems. The prooxidant effect of homocysteine and homocysteic acid on cell structures can be realized via both the glutamate receptors [3, 4] and the activation of NO synthase or inhibition of Na/KATPase, as was demonstrated for the vascular endothelium [5, 6]. It is known that erythrocytes are capable of accumulating homocysteine and excreting it into the extracellular medium [7, 8]. Erythrocytes constitute the main part of blood cells; correspondingly, the toxic effect of homocysteine and HCA may cover these cells as well. However, the effect of these compounds on the erythrocyte stability has not been studied. The goal of this work was to analyze the effect of HCA on human erythrocytes and to assess the effect of carnosine on the oxidative stress in erythrocytes caused by HCA. Various factors can cause erythrocyte hemolysis, including a decreased ambient osmotic pressure, decreased pH, and oxidants [10‐12]. The resistance of erythrocytes to hemolytic action is an integral parameter characterizing their integrity and viability as well as a criterion of their physiologically native state. Two models of hemolysis were used in this work, namely, the osmotic hemolysis and the hemolysis caused by hydrochloric acid. The former takes place with a decrease in the tonicity of medium produced by diluting cell suspension with distilled water. In this process, cells swell with subsequent disruption of the cell membrane. The latter is induced by supplementing cell suspension with hydrochloric acid, which leads to a decrease in the pH in the cytoplasm, impairments in the cytoskeleton structure, and, eventually, cell swelling and destruction [13].

Vascular Pharmacology, 2012

ABSTRACT

Neurochemistry International, 2007

N-Methyl-D-aspartate (NMDA)-activated glutamate receptors are expressed in lymphocytes, but their... more N-Methyl-D-aspartate (NMDA)-activated glutamate receptors are expressed in lymphocytes, but their roles have not yet been defined. We show that incubation of human peripheral blood lymphocytes with NMDA resulted in increased intracellular calcium and reactive oxygen species (ROS) levels through effects on NMDA-activated glutamate receptors. In terms of ROS production, T cells were most affected, followed by NK cells, whereas B cell ROS levels were not increased. In unstimulated T and NK cells, interferon-g (IFN-g) production was unaffected by NMDA, whereas interleukin-2 stimulation of IFN-g production was significantly suppressed by NMDA. Simultaneous incubation of the cells with NMDA and IL-2 resulted in a dramatic increase in the amount of cells expressing the NR1 subunit of the NMDA-activated receptors. We conclude that NMDAactivated glutamate receptor activation, accompanied by the changes in intracellular calcium and ROS levels, may be involved in the modification of immune functions of human T and NK cells.

European Neuropsychopharmacology, 2003

Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 1995

The effect of carnosine and related compounds on the luminol-and lucigenin-dependent luminescence... more The effect of carnosine and related compounds on the luminol-and lucigenin-dependent luminescence of rabbit leukocytes, activated by BaSO4, has been studied. Carnosine was found to modify BaSO4-induced chemiluminescence of leukocytes via suppression of hypochlorous anion generation with simultaneous stimulation the system of oxygen superoxide anion. Additionally to this effect carnosine prevents enzymic dismutation of O~. Auserine, acetylanserine, and homocarnosine also possess the ability to activate O~ production by leukocytes. The effect is not inherent to imidazole used in the same concentrations. Suppression of myeloperoxidase reaction by carnosine and related compounds is explained by both inhibiting action on the enzyme itself, and direct neutralization of hypochlorous anion due to formation of stable chloroamine complexes. Methylation of carnosine at N 1 nitrogen of imidazole ring, leading to anserine, forced inhibition of myeloperoxidase system, whereas its acetylation at the free 15-amino group weakened this effect.

Chemical Senses, 2005

The gustatory system is essential for almost all animals. However, the signal transduction mechan... more The gustatory system is essential for almost all animals. However, the signal transduction mechanisms have not yet been fully elucidated. We isolated labellar chemosensilla from blowfly, Phormia regina, and purified calcium binding proteins from the water soluble fraction. The most abundant calcium-binding protein was calmodulin. To investigate the role of calmodulin in taste transduction, electrophysiological responses were recorded with the calmodulin inhibitor, W-7. When we stimulated the labellar chemosensillum with sucrose plus W-7, a dose-dependent decrease of impulse frequency was observed when the concentration was <50 lM. In addition, when W-7 at 50 lM or higher concentration was added, an initial short-term impulse generation from the sugar receptor cell was observed, but this was followed by a silent period. When the sensillum was stimulated with W-7 plus a membrane-permeable cGMP analog, dibtyryl-cGMP or 8-bromo-cGMP, impulses of the sugar receptor cell were induced but the frequency was decreased. By the sidewall-recording method, we observed that the receptor potential induced by sucrose stimulation was decreased by W-7 in the sugar receptor cell, and corresponded with a disappearance of impulses. These data strongly suggest that the cGMP-gated channel generating receptor potential in the sugar receptor cell requires calmodulin for its gating.

Cellular and Molecular Neurobiology, 2010

Two novel derivatives of carnosine-(S)-trolox-L-carnosine (STC) and (R)-trolox-L-carnosine (RTC) ... more Two novel derivatives of carnosine-(S)-trolox-L-carnosine (STC) and (R)-trolox-L-carnosine (RTC) are characterized in terms of their antioxidant and membranestabilizing activities as well as their resistance to serum carnosinase. STC and RTC were synthesized by N-acylation of L-carnosine with (S)-and (R)-trolox, respectively. STC and RTC were found to react more efficiently with 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and protect serum lipoproteins from Fe 2?-induced oxidation more successfully than carnosine and trolox. At the same time, STC, RTC and trolox suppressed oxidative hemolysis of red blood cells (RBC) less efficiently than carnosine taken in the same concentration. When oxidative stress was induced in suspension of cerebellum granule cells by their incubation with N-methyl-Daspartate (NMDA), or hydrogen peroxide (H 2 O 2), both STC and RTC more efficiently decreased accumulation of reactive oxygen species (ROS) than carnosine and trolox. Both STC and RTC were resistant toward hydrolytic degradation by human serum carnosinase. STC and RTC were concluded to demonstrate higher antioxidant capacity and better ability to prevent cerebellar neurons from ROS accumulation than their precursors, carnosine and trolox.

Cell Biochemistry and Function, 2011

Incubation of rat lymphocytes with homocysteine (HC) or homocysteic acid (HCA) was found to incre... more Incubation of rat lymphocytes with homocysteine (HC) or homocysteic acid (HCA) was found to increase the stationary levels of free radicals in lymphocytes, the effect of both ligands being mediated by ionotropic receptors activated by N-methyl-D-aspactic acid (NMDA), the expression of which on rat lymphocyte membranes was earlier demonstrated. In agreement with these data, increase of free radicals in the lymphocyte cytoplasm is preceded by an increase in the intracellular calcium levels, activation of protein kinase C, nicotinamide adenine dinucleotide phosphate oxidase and/or nitric oxide synthase. Both HC and HCA increase the production of IFN-γ and TNF-α by lymphocytes and antagonist of NMDA receptors; MK-801 prevents this effect. The data presented show that rat lymphocyte membrane contains functionally active NMDA receptors, which regulate cytokine accumulation.

Bulletin of Experimental Biology and Medicine, 1994

The effect of carnosine and its natural derivatives on the generation of reactive oxygen species ... more The effect of carnosine and its natural derivatives on the generation of reactive oxygen species by leukocytes and on the myeloperoxidase reaction was studied. The chemiluminescence of samples in the course of cell activation was measured in the presence of luminol or lucigenin. Carnosine was found to produce a two-way effect, i.e., neutralization of singlet oxygen and hypochlorite anion simultaneously with activation of the system of superoxide-anion generation.

Bulletin of Experimental Biology and Medicine, 2004

We studied the effect of natural dipeptide carnosine on phagocytosis, respiratory burst in neutro... more We studied the effect of natural dipeptide carnosine on phagocytosis, respiratory burst in neutrophils, and subpopulation composition of lymphocytes from healthy donors and alcoholic patients. Carnosine in vitro produced different effects on immunocompetent cells from healthy donors and patients with alcoholism. In patients with alcoholism phagocytic activity of leukocytes and generation of reaction oxygen species increased under the influence of carnosine in a concentration of 0.01 mM, but decreased after treatment with this compound in a concentration of 1 raM. Carnosine in both concentrations stimulated the respiratory burst, but had no effect on the count of phagocytic cells in healthy donors. Carnosine in a concentration of 0.01 mM increased the number of lymphocytes carrying apoptosis markers (CD95") in patients with alcoholism not receiving therapy. Our results indicate that carnosine holds much promise for the therapy of alcoholism.

Bulletin of Experimental Biology and Medicine, 2004

We studied the effect of natural dipeptide carnosine on phagocytosis, respiratory burst in neutro... more We studied the effect of natural dipeptide carnosine on phagocytosis, respiratory burst in neutrophils, and subpopulation composition of lymphocytes from healthy donors and alcoholic patients. Carnosinein vitro produced different effects on immunocompetent cells from healthy donors and patients with alcoholism. In patients with alcoholism phagocytic activity of leukocytes and generation of reaction oxygen species increased under the influence of carnosine

Biochemical and Biophysical Research Communications, 2004

RT-PCR demonstrated that ionotropic (iGluR NR1) and metabotropic (mGluR Group III) glutamate rece... more RT-PCR demonstrated that ionotropic (iGluR NR1) and metabotropic (mGluR Group III) glutamate receptors are expressed in rodent lymphocytes. Flow cytometry showed that activation of iGluR NR1 by N-methyl-D D-aspartate (NMDA) increased intracellular free calcium and reactive oxygen species (ROS) levels and activated caspase-3. The latter effect was attenuated by the NMDA antagonist, 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), by the antioxidant N-acetylcysteine and by cyclosporin A. Treatment with L L-2-amino-4-phosphonobutyric acid (L L-AP4), an mGluR Group III agonist, increased lymphocyte ROS levels but to a lower extent than did NMDA. Activation of lymphocytes with both NMDA and L L-AP4 caused a synergistic increase in ROS levels and induced necrotic cellular death without elevating the caspase-3 activation observed in the presence of NMDA alone. These results show that lymphocyte iGluR NR1 and mGluR Group III receptors may be involved in controlling rodent lymphocyte functions and longevity as they regulate events in cell proliferation, maturation, and death.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2000

The effects of ethanol and acetaldehyde on the hemolytic stability of rabbit erythrocytes have be... more 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 hemolysed 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.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2006

Analysis of the oxidative modification of plasma and erythrocyte ghost proteins of chronic alcoho... more Analysis of the oxidative modification of plasma and erythrocyte ghost proteins of chronic alcoholic subjects and healthy non-alcoholics has been performed. It was found that increased levels of protein carbonyls in both plasma and erythrocyte ghosts from alcoholic subjects occurred in comparison to the levels found in preparations from non-alcoholics. Plasma proteins from alcoholic subjects did not show evidence of crosslinking, although plasma protein concentration and composition were changed. In alcoholic subjects who displayed no evidence of abnormal erythrocyte morphology no cross-linking of erythrocyte ghost proteins was detectable, whereas the ghosts obtained from alcoholic subjects who displayed morphologically abnormal erythrocytes contained cross-linked proteins. The in vitro treatment with acetaldehyde of erythrocytes from non-alcoholics caused increased levels of protein carbonyls and cross-linking products in erythrocyte ghost preparations which were similar to those found in severe alcoholics. It is concluded that chronic alcohol consumption can cause abnormal erythrocyte morphology and increased erythrocyte fragility as a result of oxidation and cross-linking of erythrocyte ghost proteins. These effects can be ascribed, in part, to exposure of erythrocytes to circulatory acetaldehyde which is a product of ethanol metabolism.

Annals of the New York Academy of Sciences, 1997

Neurochemical …, 2008

Prenatal hyperhomocysteinemia induced in rats by overloading of dietary methionine (1 g/kg body m... more Prenatal hyperhomocysteinemia induced in rats by overloading of dietary methionine (1 g/kg body mass daily) results in systemic disordering in progeny related to an increase in the excitotoxic feature of NMDA-receptors in cerebellar neurons and memory suppression. Administration of carnosine (100 mg/kg body mass daily) in the diet of pregnant rats with hyperhomocysteinemia prevents both cognitive function in pups and protects cerebellar neurons from oxidative stress. The effect of carnosine is accompanied by with the restoration of superoxide dismutase in rat brain, which is decreased during hyperhomocysteinemia from 2.07 units (control) to 1.54 units.

Cellular and Molecular Neurobiology, 1997

1. Carnosine, anserine, and homocarnosine are endogenous dipeptides concentrated in brain and mus... more 1. Carnosine, anserine, and homocarnosine are endogenous dipeptides concentrated in brain and muscle whose biological functions remain in doubt. 2. We have tested the hypothesis that these compounds function as endogenous protective substances against molecular and cellular damage from free radicals, using two isolated enzyme systems and two models of ischemic brain injury. Carnosine and homocarnosine are both effective in activating brain Na, K-ATPase measured under optimal conditions and in reducing the loss of its activity caused by incubation with hydrogen peroxide. 3. In contrast, all three endogenous dipeptides cause a reduction in the activity of brain tyrosine hydroxylase, an enzyme activated by free radicals. In hippocampal brain slices subjected to ischemia, carnosine increased the time to loss of excitability. 4. In in vivo experiments on rats under experimental hypobaric hypoxia, carnosine increased the time to loss of ability to stand and breath and decreased the time t...

Vascular Pharmacology

ABSTRACT

Biochemistry. Biokhimii͡a, 2000

The stability of rabbit erythrocytes to hemolysis induced by different compounds in the presence ... more The stability of rabbit erythrocytes to hemolysis induced by different compounds in the presence or absence of ethanol or acetaldehyde has been analyzed. Ethanol slightly reduced erythrocyte stability against acidic hemolysis only after long-term preincubation, but the effect of ethanol on stability to oxidative hemolysis manifested itself immediately after its addition to the cells. Ethanol decreased both stability of cells to oxidative damage and dispersion of the hemolytic curve. Comparison of the effects of ethanol and acetaldehyde showed that the destabilizing effect of ethanol might be caused by either its direct action or the effect of its metabolites formed during preincubation of ethanol with erythrocytes. Possible mechanisms of ethanol and acetaldehyde effects on erythrocyte stability are discussed.

Neurochemical Journal, 2008

Prenatal hyperhomocysteinemia induced in rats by overloading of dietary methionine (1 g/kg body m... more Prenatal hyperhomocysteinemia induced in rats by overloading of dietary methionine (1 g/kg body mass daily) results in systemic disordering in progeny related to an increase in the excitotoxic feature of NMDA-receptors in cerebellar neurons and memory suppression. Administration of carnosine (100 mg/kg body mass daily) in the diet of pregnant rats with hyperhomocysteinemia prevents both cognitive function in pups and protects cerebellar neurons from oxidative stress. The effect of carnosine is accompanied by with the restoration of superoxide dismutase in rat brain, which is decreased during hyperhomocysteinemia from 2.07 units (control) to 1.54 units.

Doklady Biochemistry and Biophysics, 2008

In this work, we demonstrate that homocysteic acid provokes oxidative stress in erythrocytes and ... more In this work, we demonstrate that homocysteic acid provokes oxidative stress in erythrocytes and decreases their hemolytic resistance, whereas the natural antioxidant carnosine [9] protects erythrocytes from its toxic effect. The discovered property can be used for development of new methods for protecting erythrocytes in hyperhomocysteinemia. Homocysteine and homocysteic acid (HCA), the product of spontaneous homocysteine oxidation, are important risk factors for neurodegenerative and cardiovascular diseases [1]. These compounds induce oxidative stress in brain neurons [2, 3] and lymphocytes [4], resulting from their toxic effect on the nervous and immune systems. The prooxidant effect of homocysteine and homocysteic acid on cell structures can be realized via both the glutamate receptors [3, 4] and the activation of NO synthase or inhibition of Na/KATPase, as was demonstrated for the vascular endothelium [5, 6]. It is known that erythrocytes are capable of accumulating homocysteine and excreting it into the extracellular medium [7, 8]. Erythrocytes constitute the main part of blood cells; correspondingly, the toxic effect of homocysteine and HCA may cover these cells as well. However, the effect of these compounds on the erythrocyte stability has not been studied. The goal of this work was to analyze the effect of HCA on human erythrocytes and to assess the effect of carnosine on the oxidative stress in erythrocytes caused by HCA. Various factors can cause erythrocyte hemolysis, including a decreased ambient osmotic pressure, decreased pH, and oxidants [10‐12]. The resistance of erythrocytes to hemolytic action is an integral parameter characterizing their integrity and viability as well as a criterion of their physiologically native state. Two models of hemolysis were used in this work, namely, the osmotic hemolysis and the hemolysis caused by hydrochloric acid. The former takes place with a decrease in the tonicity of medium produced by diluting cell suspension with distilled water. In this process, cells swell with subsequent disruption of the cell membrane. The latter is induced by supplementing cell suspension with hydrochloric acid, which leads to a decrease in the pH in the cytoplasm, impairments in the cytoskeleton structure, and, eventually, cell swelling and destruction [13].

Vascular Pharmacology, 2012

ABSTRACT

Neurochemistry International, 2007

N-Methyl-D-aspartate (NMDA)-activated glutamate receptors are expressed in lymphocytes, but their... more N-Methyl-D-aspartate (NMDA)-activated glutamate receptors are expressed in lymphocytes, but their roles have not yet been defined. We show that incubation of human peripheral blood lymphocytes with NMDA resulted in increased intracellular calcium and reactive oxygen species (ROS) levels through effects on NMDA-activated glutamate receptors. In terms of ROS production, T cells were most affected, followed by NK cells, whereas B cell ROS levels were not increased. In unstimulated T and NK cells, interferon-g (IFN-g) production was unaffected by NMDA, whereas interleukin-2 stimulation of IFN-g production was significantly suppressed by NMDA. Simultaneous incubation of the cells with NMDA and IL-2 resulted in a dramatic increase in the amount of cells expressing the NR1 subunit of the NMDA-activated receptors. We conclude that NMDAactivated glutamate receptor activation, accompanied by the changes in intracellular calcium and ROS levels, may be involved in the modification of immune functions of human T and NK cells.

European Neuropsychopharmacology, 2003

Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, 1995

The effect of carnosine and related compounds on the luminol-and lucigenin-dependent luminescence... more The effect of carnosine and related compounds on the luminol-and lucigenin-dependent luminescence of rabbit leukocytes, activated by BaSO4, has been studied. Carnosine was found to modify BaSO4-induced chemiluminescence of leukocytes via suppression of hypochlorous anion generation with simultaneous stimulation the system of oxygen superoxide anion. Additionally to this effect carnosine prevents enzymic dismutation of O~. Auserine, acetylanserine, and homocarnosine also possess the ability to activate O~ production by leukocytes. The effect is not inherent to imidazole used in the same concentrations. Suppression of myeloperoxidase reaction by carnosine and related compounds is explained by both inhibiting action on the enzyme itself, and direct neutralization of hypochlorous anion due to formation of stable chloroamine complexes. Methylation of carnosine at N 1 nitrogen of imidazole ring, leading to anserine, forced inhibition of myeloperoxidase system, whereas its acetylation at the free 15-amino group weakened this effect.

Chemical Senses, 2005

The gustatory system is essential for almost all animals. However, the signal transduction mechan... more The gustatory system is essential for almost all animals. However, the signal transduction mechanisms have not yet been fully elucidated. We isolated labellar chemosensilla from blowfly, Phormia regina, and purified calcium binding proteins from the water soluble fraction. The most abundant calcium-binding protein was calmodulin. To investigate the role of calmodulin in taste transduction, electrophysiological responses were recorded with the calmodulin inhibitor, W-7. When we stimulated the labellar chemosensillum with sucrose plus W-7, a dose-dependent decrease of impulse frequency was observed when the concentration was <50 lM. In addition, when W-7 at 50 lM or higher concentration was added, an initial short-term impulse generation from the sugar receptor cell was observed, but this was followed by a silent period. When the sensillum was stimulated with W-7 plus a membrane-permeable cGMP analog, dibtyryl-cGMP or 8-bromo-cGMP, impulses of the sugar receptor cell were induced but the frequency was decreased. By the sidewall-recording method, we observed that the receptor potential induced by sucrose stimulation was decreased by W-7 in the sugar receptor cell, and corresponded with a disappearance of impulses. These data strongly suggest that the cGMP-gated channel generating receptor potential in the sugar receptor cell requires calmodulin for its gating.

Cellular and Molecular Neurobiology, 2010

Two novel derivatives of carnosine-(S)-trolox-L-carnosine (STC) and (R)-trolox-L-carnosine (RTC) ... more Two novel derivatives of carnosine-(S)-trolox-L-carnosine (STC) and (R)-trolox-L-carnosine (RTC) are characterized in terms of their antioxidant and membranestabilizing activities as well as their resistance to serum carnosinase. STC and RTC were synthesized by N-acylation of L-carnosine with (S)-and (R)-trolox, respectively. STC and RTC were found to react more efficiently with 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and protect serum lipoproteins from Fe 2?-induced oxidation more successfully than carnosine and trolox. At the same time, STC, RTC and trolox suppressed oxidative hemolysis of red blood cells (RBC) less efficiently than carnosine taken in the same concentration. When oxidative stress was induced in suspension of cerebellum granule cells by their incubation with N-methyl-Daspartate (NMDA), or hydrogen peroxide (H 2 O 2), both STC and RTC more efficiently decreased accumulation of reactive oxygen species (ROS) than carnosine and trolox. Both STC and RTC were resistant toward hydrolytic degradation by human serum carnosinase. STC and RTC were concluded to demonstrate higher antioxidant capacity and better ability to prevent cerebellar neurons from ROS accumulation than their precursors, carnosine and trolox.

Cell Biochemistry and Function, 2011

Incubation of rat lymphocytes with homocysteine (HC) or homocysteic acid (HCA) was found to incre... more Incubation of rat lymphocytes with homocysteine (HC) or homocysteic acid (HCA) was found to increase the stationary levels of free radicals in lymphocytes, the effect of both ligands being mediated by ionotropic receptors activated by N-methyl-D-aspactic acid (NMDA), the expression of which on rat lymphocyte membranes was earlier demonstrated. In agreement with these data, increase of free radicals in the lymphocyte cytoplasm is preceded by an increase in the intracellular calcium levels, activation of protein kinase C, nicotinamide adenine dinucleotide phosphate oxidase and/or nitric oxide synthase. Both HC and HCA increase the production of IFN-γ and TNF-α by lymphocytes and antagonist of NMDA receptors; MK-801 prevents this effect. The data presented show that rat lymphocyte membrane contains functionally active NMDA receptors, which regulate cytokine accumulation.

Bulletin of Experimental Biology and Medicine, 1994

The effect of carnosine and its natural derivatives on the generation of reactive oxygen species ... more The effect of carnosine and its natural derivatives on the generation of reactive oxygen species by leukocytes and on the myeloperoxidase reaction was studied. The chemiluminescence of samples in the course of cell activation was measured in the presence of luminol or lucigenin. Carnosine was found to produce a two-way effect, i.e., neutralization of singlet oxygen and hypochlorite anion simultaneously with activation of the system of superoxide-anion generation.

Bulletin of Experimental Biology and Medicine, 2004

We studied the effect of natural dipeptide carnosine on phagocytosis, respiratory burst in neutro... more We studied the effect of natural dipeptide carnosine on phagocytosis, respiratory burst in neutrophils, and subpopulation composition of lymphocytes from healthy donors and alcoholic patients. Carnosine in vitro produced different effects on immunocompetent cells from healthy donors and patients with alcoholism. In patients with alcoholism phagocytic activity of leukocytes and generation of reaction oxygen species increased under the influence of carnosine in a concentration of 0.01 mM, but decreased after treatment with this compound in a concentration of 1 raM. Carnosine in both concentrations stimulated the respiratory burst, but had no effect on the count of phagocytic cells in healthy donors. Carnosine in a concentration of 0.01 mM increased the number of lymphocytes carrying apoptosis markers (CD95") in patients with alcoholism not receiving therapy. Our results indicate that carnosine holds much promise for the therapy of alcoholism.

Bulletin of Experimental Biology and Medicine, 2004

We studied the effect of natural dipeptide carnosine on phagocytosis, respiratory burst in neutro... more We studied the effect of natural dipeptide carnosine on phagocytosis, respiratory burst in neutrophils, and subpopulation composition of lymphocytes from healthy donors and alcoholic patients. Carnosinein vitro produced different effects on immunocompetent cells from healthy donors and patients with alcoholism. In patients with alcoholism phagocytic activity of leukocytes and generation of reaction oxygen species increased under the influence of carnosine

Biochemical and Biophysical Research Communications, 2004

RT-PCR demonstrated that ionotropic (iGluR NR1) and metabotropic (mGluR Group III) glutamate rece... more RT-PCR demonstrated that ionotropic (iGluR NR1) and metabotropic (mGluR Group III) glutamate receptors are expressed in rodent lymphocytes. Flow cytometry showed that activation of iGluR NR1 by N-methyl-D D-aspartate (NMDA) increased intracellular free calcium and reactive oxygen species (ROS) levels and activated caspase-3. The latter effect was attenuated by the NMDA antagonist, 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), by the antioxidant N-acetylcysteine and by cyclosporin A. Treatment with L L-2-amino-4-phosphonobutyric acid (L L-AP4), an mGluR Group III agonist, increased lymphocyte ROS levels but to a lower extent than did NMDA. Activation of lymphocytes with both NMDA and L L-AP4 caused a synergistic increase in ROS levels and induced necrotic cellular death without elevating the caspase-3 activation observed in the presence of NMDA alone. These results show that lymphocyte iGluR NR1 and mGluR Group III receptors may be involved in controlling rodent lymphocyte functions and longevity as they regulate events in cell proliferation, maturation, and death.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2000

The effects of ethanol and acetaldehyde on the hemolytic stability of rabbit erythrocytes have be... more 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 hemolysed 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.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2006

Analysis of the oxidative modification of plasma and erythrocyte ghost proteins of chronic alcoho... more Analysis of the oxidative modification of plasma and erythrocyte ghost proteins of chronic alcoholic subjects and healthy non-alcoholics has been performed. It was found that increased levels of protein carbonyls in both plasma and erythrocyte ghosts from alcoholic subjects occurred in comparison to the levels found in preparations from non-alcoholics. Plasma proteins from alcoholic subjects did not show evidence of crosslinking, although plasma protein concentration and composition were changed. In alcoholic subjects who displayed no evidence of abnormal erythrocyte morphology no cross-linking of erythrocyte ghost proteins was detectable, whereas the ghosts obtained from alcoholic subjects who displayed morphologically abnormal erythrocytes contained cross-linked proteins. The in vitro treatment with acetaldehyde of erythrocytes from non-alcoholics caused increased levels of protein carbonyls and cross-linking products in erythrocyte ghost preparations which were similar to those found in severe alcoholics. It is concluded that chronic alcohol consumption can cause abnormal erythrocyte morphology and increased erythrocyte fragility as a result of oxidation and cross-linking of erythrocyte ghost proteins. These effects can be ascribed, in part, to exposure of erythrocytes to circulatory acetaldehyde which is a product of ethanol metabolism.

Annals of the New York Academy of Sciences, 1997

Neurochemical …, 2008

Prenatal hyperhomocysteinemia induced in rats by overloading of dietary methionine (1 g/kg body m... more Prenatal hyperhomocysteinemia induced in rats by overloading of dietary methionine (1 g/kg body mass daily) results in systemic disordering in progeny related to an increase in the excitotoxic feature of NMDA-receptors in cerebellar neurons and memory suppression. Administration of carnosine (100 mg/kg body mass daily) in the diet of pregnant rats with hyperhomocysteinemia prevents both cognitive function in pups and protects cerebellar neurons from oxidative stress. The effect of carnosine is accompanied by with the restoration of superoxide dismutase in rat brain, which is decreased during hyperhomocysteinemia from 2.07 units (control) to 1.54 units.

Cellular and Molecular Neurobiology, 1997

1. Carnosine, anserine, and homocarnosine are endogenous dipeptides concentrated in brain and mus... more 1. Carnosine, anserine, and homocarnosine are endogenous dipeptides concentrated in brain and muscle whose biological functions remain in doubt. 2. We have tested the hypothesis that these compounds function as endogenous protective substances against molecular and cellular damage from free radicals, using two isolated enzyme systems and two models of ischemic brain injury. Carnosine and homocarnosine are both effective in activating brain Na, K-ATPase measured under optimal conditions and in reducing the loss of its activity caused by incubation with hydrogen peroxide. 3. In contrast, all three endogenous dipeptides cause a reduction in the activity of brain tyrosine hydroxylase, an enzyme activated by free radicals. In hippocampal brain slices subjected to ischemia, carnosine increased the time to loss of excitability. 4. In in vivo experiments on rats under experimental hypobaric hypoxia, carnosine increased the time to loss of ability to stand and breath and decreased the time t...