[Differences between cerebellum and hippocampus in antioxidant system].

The effect of portacaval shunting on the antioxidant status of the cerebellum and hippocampus was studied in rats using standard methods of enzymatic analysis. Endogenous ammonia levels and activities of eight antioxidant enzymes were shown to be unequal in two brain regions and to respond differently upon portal-systemic shunt surgery.

[Effects of amyloid-ß peptide Aß(25-35) on glycolytic and antioxidant enzymes of different ages].

Amyloid-ß peptide Aß(25-35) was shown to cause lysis of rat erythrocytes of different ages. The toxicity of Aß(25-35) positively correlated with both the erythrocyte age andthe peptide concentration. The activity of glycolytic, antioxidant, and Na+/K(+)-ATPase enzymes decreased with erythrocyte aging in vivo. In vitro Aß(25-35) reduced the activity of hexokinase, phosphofructokinase, pyruvate kinase, glutathione peroxidase, and glutathione transferase and increased Na+/K(+)-ATPase activity in aged erythrocytes to a greater degree than in young cells.

Argocytes containing enzyme nanoparticles reduce toxic concentrations of arginine in the blood.

A method for incorporation of arginase nanoparticles into mouse erythrocytes has been developed and the possibility of reducing blood arginine concentration in animals with experimental hyperargininemia with arginase-loaded erythrocytes (argocytes) has been studied. Argocyte infusion to animals with hyperargininemia led to a rapid decrease in blood arginine concentration within 1 h and this effect of argocytes persisted for at least 4 h. This was paralleled by an increase in plasma concentrations of urea and ornithine. Hence, plasma arginine is hydrolyzed by arginase incorporated into argocytes; argocytes are functionally active and can serve as a defense system in pathological hyperargininemia, while the method developed by us can be regarded as a new nanobiotechnology for medicine and veterinary.

Experiments on alcocytes containing enzyme nanoparticles for reducing toxic blood concentration of ethanol.

We developed a method of introduction of alcohol dehydrogenase and aldehyde dehydrogenase into mouse and human erythrocytes. The possibility of using erythrocytes loaded with the two enzymes (alcocytes) for reducing ethanol concentration in animal blood was studied. Injection of alcocytes to mice led to accelerated decrease in ethanol concentration as soon as after 5 min and this capacity of alcocytes persisted for at least 2 h. Alcocytes prepared from fresh or preserved human blood did not survive in mice. Thus autologous alcocytes is functionally active and can be used as a protective system in acute alcohol intoxication. The developed method can be regarded as a new medical biotechnology.

[Arginase, nitrates, and nitrites in the blood plasma and erythrocytes in hypertension and after therapy with lisinopril and simvastatin].

Arginase activity in erythrocytes is higher in patients with arterial hypertension and atherosclerosis as compared with healthy people. Therapy with either lisinopril alone or in combination with simvastatin for 3-6 months causes a decrease in the arginase activity to the control level. Both the monotherapy and the combination therapy increased the concentrations of NO2(-), NO3(-), and total NOO2(-) + NO3(-)in the plasma of hypertensive patients. The NO2(-) + NO3(-) concentration in erythrocytes decreases in hypertensive patients but is completely restored after therapy with lisinopril alone or in combination with simvastatin. Thus, lisinopril and lisinopril plus simvastatin display a pronounced and equal normalizing effect on arginase activity in human erythrocytes, which is elevated in hypertension, as well as on the endothelial nitric oxide synthase activity, which is decreased in hypertension.

[Antioxidant enzymes in erythrocytes from hypertension patients receiving lisinopril monotherapy or combined lisinopril plus simvastatin therapy].

Statins and angiotensin-converting enzyme (ACE) inhibitors have beneficial impact on the serum cholesterol and blood pressure. It is supposed that statins and ACE inhibitors may modify the antioxidative status of erythrocytes. The study objective was to compare the effects of two treatments, lisinopril alone vs lisinopril plus simvastatin, on erythrocyte antioxidant enzyme activities. The study involved 32 patients with arterial hypertension, the initial serum total cholesterol, LDL-cholesterol and triglycerides within the normal range. Patients of two groups, each of 16 subjects, were treated with lisinopril (10 mg/day) or with lisinopril (10 mg/day) plus simvastatin (20 mg/day). Before and after 3 and 6 months of follow-up therapy, activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GLR) in purified erythrocytes were determined. In all patients, significantly higher catalase activity (by 79.3-106.5%, p < 0.0001) and significantly lower GPx activity (by 20.7-30.6%, p < 0.001) were observed after therapy as compared to the baselines. Just the same results were obtained in both groups (lisinopril and lisinopril + simvastatin), after both periods (3 and 6 month) of treatments. SOD activity was increased only in the lisinopril group and only after 6 months (p = 0.0345). No changes of GLR reductase activity were seen under all conditions indicated. Thus, the lisinopril monotherapy and combined lisinopril plus simvastatin therapy exhibit specific, pronounced and equipotent effects on antioxidant enzymes in human erythrocytes. Administration of lisinopril or lisinopril plus simvastatin may protect erythrocytes and other tissues from oxidative damage.

Activation of AMP deaminase and adenosine deaminase in the liver during ammonia poisoning and hepatitis.

We studied the effect of acute ammonia poisoning and CCl4-induced subacute hepatitis on activities of AMP deaminase and adenosine deaminase in rat liver. Both models of liver failure were accompanied by an increase in activities of AMP deaminase and adenosine deaminase in the cytoplasmic fraction of the liver (by 2.4-4.2 times compared to the control). A direct correlation was found between activities of AMP deaminase and adenosine deaminase. We believe that two parallel pathways of AMP degradation are activated simultaneously, which leads to rapid depletion of adenylate reserves under pathological conditions.

[The drug hypoxen--a new inhibitor of mitochondrial respiration and mitochondrial dehydrogenases].

The effect of hypoxen on the oxygen consumption and activity of dehydrogenases in rat liver mitochondria has been studied. The addition of hypoxen to mitochondria caused a speed reduction of phosphorylating and uncoupling respiration. The minimal effective concentration of hypoxen was 15 microg/ml with succinate, 60 microg/ml with pyruvate or palmitoylcarnitine, and 120 microg/ml with glutamate as the substrates. The activities of malate, glutamate, and succinate dehydrogenases in mitochondria were significantly decreased by the effect of hypoxen.

[Effect of the beta-amyloid peptide Abeta25-35 and fullerene C60 on the activity of enzymes in erythrocytes].

The effect of the beta-amyloid peptide Abeta25-35 and fullerene C60 on the activity of the cytoplasmic enzymes lactate dehydrogenase (LDH) and glutathione peroxidase (GLP), and membrane-bound phosphofructokinase (PFK) and Na+,K(+)-ATPase in human erythrocytes has been studied. When used in combination, the cytotoxins decrease the activity of LDH and PFK in a nonadditive manner; in this case, Abeta25-35 protects PFK against the inhibitory effect of C60. The activity of LDH, GLP, and PFK decreases within the first 2-20 min of incubation of erythrocytes with Abeta25-35 in the absence of glucose. The addition of glucose sharply decreases the inhibitory action of Abeta25-35 on LDH and GLP but does not affect the fourfold decrease in activity of PFK; the activity of membrane-bound Na+,K(+)-ATPase does not depend on the presence of glucose. Possible mechanisms of interaction of Abeta25-35 and fullerene C60 with the erythrocyte membrane and enzymes are discussed.

[Role of glycolysis and antioxidant enzymes in the toxicity of amyloid beta peptide Abeta25-35 to erythrocytes].

The role of glycolysis and antioxidant enzymes in amyloid beta peptide Abeta(25-35) toxicity to human and rat erythrocytes was studied. The erythrotoxicity of Abeta(25-35) was shown to increase two- to fourfold both in the absence of glucose in the incubation medium and upon the addition of sodium fluoride, an enolase inhibitor. Potassium cyanide, a Cu,Zn-superoxide dismutase inhibitor, abolishes the toxic effect of Abeta(25-35) to erythrocytes, whereas mercaptosuccinate, a glutathione peroxidase inhibitor, and ouabain, a Na+,K+-ATPase inhibitor, promote it. Sodium azide, a catalase inhibitor, did not affect the cell lysis under the action of Abeta(25-35) . The results support the hypothesis that H2O2, Cu,Zn superoxide dismutase, and glutathione peroxidase are involved in the toxicity mechanism rather than superoxide radical. Glycolysis and Na+,K+-ATPase play a substantial protective role. Fullerene C(60) nanoparticles are toxic to erythrocytes of both types; their toxicity is not related to enhanced oxidative stress and the mechanism of toxicity differs from that of Abeta(25-35) .

[Toxic effect of Abeta25-35 and fullerene C60 on erythrocytes].

Using light microscopy and spectrophotometry, it has been shown that amyloid beta-peptide Abeta25-35 and water-soluble fullerene C60 cause lysis of human and rat erythrocytes. Both fullerene C60 and Abeta25-35 partly inhibited the activities of membrane-associated phosphofructokinase and plasmalemmal lactate dehydrogenase in erythrocytes.

Studies on ammocytes: development, metabolic characteristics, and detoxication of ammonium.

The possibility of reducing ammonium concentration in the blood of mice with hyperammonemia with ammocytes (erythrocytes loaded with glutamate synthase) and the metabolic characteristics of these cells were studied. Injection of ammocytes into the blood stream of animals with hyperammonemia led to reduction of the blood ammonium concentration within the first 30-120 min and this activity of ammocytes was retained for at least 2 days. Endogenous phosphofructokinase, glucose-6-phosphate dehydrogenase, hexokinase, lactate dehydrogenase, pyruvate kinase, and Na(+),K(+)-ATPase in ammocytes remained at the levels of catalytic activities characteristic of intact erythrocytes. Hence, ammocytes are functionally active cells and can be used as a protective system in pathological hyperammonemia, while the method can be regarded as a new technology for medicine and veterinary.

Effects of hydrated forms of C60 fullerene on amyloid 1-peptide fibrillization in vitro and performance of the cognitive task.

It has been shown for the first time by transmission electron microscopy that the hydrated fullerene C60 inhibited the fibrillization of amyloid-beta25-35 peptide. The fullerene affected the amyloid-beta25-35 assembly, manifesting its anti-amyloidogenic capacity. Our in vivo investigations demonstrated also that a single intracerebroventricular injection of the C60 hydrated fullerene at a dose of 7.2 nmol/ventricle significantly improved the performance of the cognitive task in control rats. The intracerebroventricular injection of the C60 hydrated fullerene (3.6 nmol/ventricle) prevented the impairment of performance of the cognitive task induced by amyloid-beta25-35 (22.5 nmol/ventricle). The results obtained may be useful in the development of therapy of Alzheimer's disease.

[Antioxidant enzymes, hydrogen peroxide metabolism, and respiration in rat heart during experimental hyperammonemia].

The effects of toxic ammonia doses on H2O2 metabolism, energy metabolism, and antioxidant enzyme activities in rat heart were studied. Ammonium acetate administration to animals proved to increase total superoxide dismutase (SOD), catalase, and glutathione peroxidase activities in the heart cytoplasmic fraction as well as Mn-SOD, catalase, and glutathione reductase in heart mitochondria. Conversely, ammonia inhibited the same activities in the brain, liver, and erythrocytes. Hyperammonemia had no effect on the levels of ATP, ADP and total adenine nucleotides in the heart but decreased them in the brain. Ammonia impaired oxidative phosphorylation and increased the rate of H202 production in heart and brain mitochondria. The ammonia concentration inhibiting antioxidant enzymes in the liver and brain can be insufficient for such effect in the heart.

[Antioxidant enzymes of the rat liver, brain, heart and erythrocytes in ammonia intoxication].

Injection of large amounts of ammonium salts leads to rapid death of animals. However, the molecular mechanisms involved in ammonia toxicity remain to be clarified. We have tested the effect of toxic dose of ammonium acetate on the activities of antioxidant enzymes in rat liver, brain, heart and erythrocytes. Acute ammonia intoxication resulted in rapid (within 11 min) decrease in superoxide dismutase, catalase and glutathione peroxidase activities in liver and brain mitochondria and cytosol and in erythrocytes, but in increase of these enzyme activities in heart. Diminished activities of the antioxidant enzymes in liver, brain and erythrocytes suggest that the systemic oxidative stress takes place, whereas their elevated activities in heart can be the adaptive reaction to oxidative stress in hyperammoniemia.

Antioxidant status of erythrocytes after acupuncture treatment.

A course of acupuncture therapy in patients with locomotor, peripheral nervous system, gynecological, and bronchopulmonary diseases led to complete or partial normalization of nonspecifically changed MDA content, catalase and glutathione peroxidase activities in erythrocytes. SOD activity increased after therapy and did not differ from the control. Acupuncture stabilized disordered LPO processes and improved the antioxidant status of erythrocytes.

[Calcium and ammonia stimulate monoamine oxidase A activity in brain mitochondria]. / Kal'tsii i ammiak stimuliruiut aktivnost' monoaminoksidazy A v mitokhondriiakh mozga.

The effect of ammonia and calcium on the activity of monoamine oxidase (MAO) was studied. The enzyme activity in non-synaptic brain mitochondria isolated from rats administered with ammonium acetate was assayed by release of H2O2 using spectrophotometry. The effect of calcium on MAO was assayed directly after addition of Ca2+ to the non-synaptic mitochondria isolated from the forebrain of the control rats. Both ammonium acetate injection in vivo and Ca2+ addition in vitro stimulated the activity of MAO A but not that of MAO B in mitochondria. This is the first evidence that ammonia and Ca2+ regulate MAO A in non-synaptic mitochondria in the forebrain and can contribute to oxidative stress in the neurons via MAO A activation.

[Activity of antioxidant enzymes in liver and brain is decreased in the early stage of diabetes, and this decrease depends on the function of NMDA-receptors]. / Aktivnost' antiokislitel'nykh fermentov v pecheni i mozge snizhaetsia vrannie sroki diabeta, i éto snizhenie zavisit ot funktsionirovaniia NMDA-retseptorov.

Antioxidant enzyme activities in rat liver and forebrain and the effect of the MK-801 administration on these activities were estimated on 6th day of alloxan-induced diabetes. The catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase activities of cytosolic fractions from both liver and forebrain were shown to decrease significantly in prediabetic rats, and these alterations were virtually prevented by the course of MK-801 administration. The results suggest that the suppression of antioxidant enzymes can be the primary biochemical disturbance in diabetes progression and that glutamate NMDA receptors can be involved in the molecular mechanism underlying this condition.

The stimulatory effect of negative air ions and hydrogen peroxide on the activity of superoxide dismutase.

The activity of erythrocyte cytosolic superoxide dismutase from rat, bovine, man and duck was considerably increased when measured after preparation or incubation in media pretreated with negative air ions (mostly superoxide) from electroeffluvial ion generator. 0.5-1.0 microM H2O2 was found in incubation medium after treatment with air ions. The stimulatory effect of air ions on superoxide dismutase activity was mimicked by addition of 0.5-6 microM H2O2. The primary physicochemical mechanism of beneficial biological action of negative air ions is suggested to be related to the stimulation of superoxide dismutase activity by micromolar concentrations of H2O2.