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Objective: to determine the effectiveness of citrulline use for correcting endothelial dysfunction in children resi dents of radioactively contaminated areas., Materials and Methods: A group of children residents of radioactively contaminated areas with the presence of clinical and paraclinical signs of endothelial dysfunction was selected to assess the effectiveness of correcting endothelial dysfunction by the usage of NO potential donator - citrulline according to the data of selective screen ing. There were determined the biochemical parameters of the content of NO stable metabolites, L arginine, lipid peroxidation, antioxidant enzymes in the blood serum; the indices of cellular and humoral immunity; the instrumen tal indices of vascular endothelium dependent reaction on occlusion test, the lung ventilation capacity, the bioelec tric activity of the myocardium, the autonomic regulation of the cardiovascular system.Examined children were received a course of citrulline malate., Results and Conclusions: An increased content of serum L arginine, nitrite, and amounts of NO metabolites was established in children with endothelial dysfunction who were received a course of citrulline malate. Bronchospasm elimination was noted in the significant part of examined patients after the drug use. Decreased recovery period and increased period of hypercompensation for thermographic circulation index in the test with post occlusion reac tive hyperemia were detected by an evaluation of indicators for vascular endothelium dependent vasodilatation using thermographic method indicating an increased endothelial vasomotor capacity. There was tendency to improve the processes of autonomic regulation of the heart rhythm and repolarization of the heart muscle. The antioxidant effect of used citrulline malate course was determined as: decreased content of serum LPO end products that react with thiobarbituric acid under elevated activity of antioxidant - catalase. An increase in the percentage of T lymphocyte, normalization of their subpopulation composition was noted in dynamics of citrulline malate application., (Ye. I. Stepanova, I. Ye.Kolpakov, V. M. Zygalo, V. Yu. Vdovenko, V. H. Kondrashova, O. S. Leonovich, V. V. Kryzhanivska.)

Objective: to explore possible transgeneration effects in the rats offspring of the first generation of parents subject ed to the combined effects of N stearoylethanolamine (NSE) and external exposure.Materials and metods. In the first generation rats of both sexes born to parents who have experienced the combined influence of ionizing radiation at a dose of 2.0 Gy and NSE a daily dose of 50.0 mg/kg, administered before or after exposure indicators of pro and antioxidant systems (the concentration of TBA reactive products, catalase and glu tathione peroxidase activity in plasma) were defined, concentrations of sex hormones testosterone and estradiol and nitrite anion were studied., Results: Irradiation of parents caused a three fold reduction of testosterone in the blood plasma of males progeny, increased activity of catalase in plasma of female offsprings, as well as significantly increased the concentration of protein in the offsprings' blood plasma of both sexes. Introduction of NSE to parents before exposure caused the acti vation of lipid peroxidation in plasma of both sexes offsprings' against the background of a trustworthy decrease in activity of antioxidant enzymes (catalase and glutathione peroxidase), however, prevented a sharp reduction of testosterone content in the blood plasma of males offsprings, conditioned by the influence of radiation on the body of their parents. NSE introduction to parents after exposure caused no significant violations of pro/ antioxidant bal ance in the body of both sexes progeny, but did not eliminate the negative impact of parental exposure to testos terone levels in male offsprings., Conclusion: The transgeneration impact of NSE is manifested by radio sensitizing properties in the first generation offsprings in case of application to parents before irradiation., (A. A. Chumak, V. V. Talko, N. P. Atamanyuk, L. P. Derevyanko, N. K. Rodionova, G. V. Kosyakova, A. F. Mehed, T. M. Goridko, A. G. Berdyshev, N. M. Gula.)

We investigated the role of changes in the endogenous nitric oxide (NO) metabolism during the influence of succinic acid amides as biotransformation products of an anti-diabetic drug on the state of hemostasis. In experiment with rats, synthetic succinamides were applied in quanti- ties equimolar to the sub-toxic dose of the pharmaceutical substance. We investigated the indicators characterizing the state of platelet and coagulation hemostasis in the blood plasma, the content of the stable NO metabolites and the activity of nitrogen oxide synthase (NOS) in the liver homogenate, blood plasma and urine of rats. We found that sub-chronic succinamides introduction reduced the nitrite and nitrate anions concentration in the blood plasma (by 30-50 and 20-35% resp.), liver (by 16-19 and 14-18%) and urine (by 50-70 and 38-55%). These changes were essentially dependent on the reduction in the NOS activity (by 33%). The studied compounds showed a 1.5 fold increase in the coagulation potential of the blood plasma and cause a 20% boost in the aggregation of thrombocytes. Analysis of the pair correlation coefficients showed positive association of the changes in indicators of the NO metabolism and hemostasis. The obtained results suggest that the registered manifestation of the pro-coagulation and thrombogenic action of succinamides applied in the sub-toxic doses is partially determined by a drop of the vasoactive NO pool that in turn, occurs due to a decline of the NOS activity.

In experiments on white male rats it was shown that repeated administrations of nitric oxide precursors L-arginine and L-arginine L-glutamate do not alter the activity of cytolysis enzymes, reduce lipid peroxidation that correlates with indices of antioxidant protection, increase enzymatic activity in mitochondria and reduce endotoxemia. NO-synthase blockade by L-NAME increases endotoxemia, inhibits detoxification process in the liver, reduces the activity of electron transport enzymes in mitochondria, activation of lipids peroxodation reducing protective reserves of antioxidant system that is accompanied by low levels of NO2- in blood and liver.

The total activity of NO-synthase and content of stable metabolitic products of nitric oxide in the peripheral blood of rats under low doses of ionizing radiation and administration of natural polyphenol complex of grape was investigated. It was found that natural polyphenol compounds of grapes have the ability to correct radioinduced changes in L-arginine/NO system. It was noted that the action of X-radiation increased activity of NO-synthase in the peripheral blood of rats. However, the consumption of natural polyphenol complex of grape led to a decrease of this index to control values. An increase in NOS activity under irradiation leads to the increase of NO stable metabolites content, which is reflected in the accumulation of nitrite- and nitrate-anions in the peripheral blood of rats. The consumption of preparation of polyphenol complex this index decreased in the early period of the experiment, and on the third day after exposure, the total content of NO stable metabolites is slightly higher compared to the indices of control animals. Thus, the ability of natural polyphenol complex to cause attenuation of oxidative-nitrative stress caused by ionizing radiation was investigated experimentally.

The influence of N-stearoylethanolamine was investigated on the activity of enzymes of antioxidant protection and content of stable metabolites of nitric oxide (NO) in the testes and plasma of rats at the early stages of development of streptozotocine-induced diabetes mellitus. It was shown that the activity of superoxide dismutase, catalase is reduced in the plasma and testes of animals with streptozotocin-induced (50 mg/kg) diabetes (blood glucose 8-10 mmol/L). A significant increase in the amount of nitrite and nitrate anions was revealed in the plasma of rats, while only the level of nitrite was significantly changed in the testes of animals. The per os administration of the NSE aqueous suspension in a dose of 50 mg/kg during 10 days to the rats with induced diabetes contributed to the normalization of catalase activity in the testis, which correlated with a decrease in the amount of TBA-reacting products and activity of superoxide dismutase and catalase in the blood plasma of animals; the use of NSE also contributed to the reduction of nitrite content in the gonads and to normalization of both nitrite and nitrate in the blood plasma of rats. The NSE administration to intact animals caused an increase in superoxide dismutase activity and significantly reduced the content of stable NO metabolites in the blood plasma of animals.

The effects of agmatine on oxidative and nonoxidative metabolic pathways of L-arginine were investigated both in plasma and erythrocytes under experimental diabetes mellitus. It was indicated, that agmatine prevents the development of oxidative-nitrosative stress in diabetic rats. After treatment of animals by agmatine NO-synthase methabolic pathway of L-arginine is depressed whereas arginase one increases in erythrocytes of rats with experimental diabetes mellitus.

There were concluded our results of animal experimental investigation and clinical observation of the quercetin-containing preparation corvitin (C) in primary glaucoma treatment. On the model of disease it is shown for rabbit, that introduction of 0.5 ml 2 % C as factious instillation into the eye a basely decreased eye blood flow was increased twice, mionectic at glaucoma eye hydrodynamics was normalized : the outflow of liquid increased on 58 %, inflow - on 52 %, intraocular pressure went down on 14%. Intravenous inflowing of C brought down expressed of oxidative stress - M[see text]A in blood is decreased on 40 %, level of endothelial dysfunction marker NO is increased on 70 %. On the model of glaucoma for rats C, entered protractedly, showed the neuroprotective actions on the neurons of retina, promoting survivability of ganglion cells, that it is shown on histological preparations. Application C in the clinic of glaucoma (intravenously a 0.5 g of preparation in 100 ml of solution) improved for patients a blood supply in the eye on 25 %, and also rendered a positive antioxidant and metabolic effect. Noted positive influences of C concurrently to important pathogeneses factors such as regional eye blood supply, eye hydrodynamics, oxidative stress, metabolic changes, survival of retina neurons grounds to talk about new strategy of pathogenesis therapy of glaucoma.

We carried out a study on elderly people (70 +/- 2,2 years old) operated on as an acute occlusion of the femoral artery at its different anatomical levels. In those people, development of oxidative stress has been shown in injured lower extremity in the process of restoring of circulation. Marked increase in catalase activity in the blood gives evidence for work of the anti-oxidative defence system with tense. We determined an increase in aspartataminotransferase, alaninaminotransferase and creatininkinase in ischemia/reperfusion which are widely used to identify injures in muscular tissues. It has been shown that NO(2-) content in the blood at reperfusion depended on the level of nitrites and the duration ofischemia. Significant changes in NO metabolite content in the blood of the patients suffering from acute occlusion injures of the arteries in the lower extremities could be related with endothelial dysfunction.

Subchronic administration of semicarbazide in the experiment with the rats was used to reduce the formaldehyde level in the organism in order to reveal the interaction between formaldehyde metabolism and biochemical parameters, which define the oxidant-antioxidant system condition and NO metabolism. It has been found that under semicarbazide impact the generation of free radicals, ROS, nitrite and nitrate were enhanced while aldehydes level was reduced that resulted from not only semicarbazide effect like the aldehydes acceptor, but the formaldehyde synthesis slowdown and acceleration of its transformation into format as well. We suppose that formaldehyde plays certain role in the development of connective tissue pathology.

14 trained and 21 non-trained girls 18-22 years of age have been inspected. We found that systematically trained girls had a higher level of nitric oxide synthesis through calcium-dependent L-arginine oxidation by constitutive NO-synthase isoforms (eNOS, nNOS) and through reduction of stable oxidized NO metabolites. NO synthesized de novo in calcium-dependent pathway provides a long-term organism adaptation to physical loads of high volume and intensity at the beginning and in the middle of stress-aggravated competition period. At the end of competition period we detected significant activation of inducible calcium-independent de novo NO synthesis from L-arginine.

Alimentary hypercholesterolemia, as well as the intensive physical loadings are accompanied diminishing of level of nitrite-anion as compared to the control group of animals. Combination of the intensive physical loadings and hypercholesterolemia results in maximal lowering level of nitrite-anion and more expressed atherosclerotic damage of wall of arteries of experimental rats, and the moderate physical loadings at hypercholesterolemia render an opposite effect.

Hypoxia causes the disruption of mitochondria electron respiratory chain, production of active oxygen forms and the unoxidative protection. In experiments on Wistar rats the influence of sodium succinate (50 mg/kg) and 6-ketoglutarate (200 mg/kg) on NO2-, NO3-, urea and polyamines contents in blood and liver under acute hypoxia (7% O2 in N2, 30 min) was investigated. Nitrite and nitrate content decreased in erythrocytes and liver but not in plasma under acute hypoxia. The exogenous succinate (SK) stimulated production of nitric oxide in erythrocytes and liver while 6-ketoglutarate (KG) only in liver. The switch from more intensive SK oxidation that reveals adrenomimetic influence and causes the synthesis and release of NO from erythrocyte, to less intensive KG correlates with well-known decrease of tissue respiration under the activation of the cholinergic system due to urea cycle activation particularly in liver. The activation of the SK oxidation takes place mainly under the different stress conditions and causes NO production in the blood cells. These conditions of the intensive and fast action under acute hypoxia are accompanied on the one hand by the increase of oxygen input ratio and on the other hand by activation of the free radical oxidation. The protective effect of the natural Krebs cycle intermediates--SK and KG in particular, is related to the regulation of NO synthesis and its metabolism in the main organs. These results proved the existence not only metabolite control of NO system by Krebs cycle intermediates, but the existence of the systemic mechanism for the support of the functional state of mitochondria under hypoxia.

A total of 28 patients with stage II hypertensive disease (HD) were examined, their age ranging between 32 to 64 years. Of these, 17 subjects were diagnosed as having had alimentary obesity. The control group comprised 11 subjects with normal level of arterial pressure and body mass. Studied in the above patients were blood serum content of nitrogen oxide by determining levels of its stable metabolites NO2- and NO3- anions. HD patients presenting with normal body weight and those with obesity demonstrated significantly lower blood serum levels of anions NO2- and NO3- as compared to healthy subjects. In HD patients, obesity is accompanied by a more significant reduction in blood serum levels of NO2- and NO3-, which fact might be caused by inhibition of nitratereductase.

The investigation was designed to study nitric oxide (NO) blood level estimated by measuring its stable metabolites nitrite (NO2-) and nitrate (NO3-) concentration in highlanders (2,200 m a.s.l.). NO2- [symbol: see text] NO3- concentration was measured with Griss reagent and brucine reagent respectively with using the spectrophotometric method. We first found that highlanders compared to lowlanders have increased blood level of NO2- (37 +/- 3.3 nmol/ml vs. 28.5 +/- 1.3 nmol/ml, P < 0.05) and NO3- (1362 +/- 43 nmol/ml vs. 845 +/- 65 nmol/ml, P < 0.001). As the most significant, there was increase in NO2- concentration in erythrocytes (by about 6 times), NO3- level in erythrocytes was revealed to be increased by 2.5 times, whereas the plasma concentration of these stable metabolites was the same (for NO3-) or even slightly decreased (for NO2-). Such increased NO stable metabolites blood level in highlanders may explain widening of vasodilative reserve and strengthening of cardiac pump and contractile functions, which we revealed previously. Activation of NO-system in high altitude is important and probable trigger adaptive mechanism of cardiovascular system to hypoxia. This mechanism allows to retain adequate tissue perfusion and optimal oxygen supply in its decreased partial pressure in inhaled air and thereby to prevent diseases caused by vasospastic processes.