[Complexes of nitric oxide with hemoglobin and paramagnetic metalloenzymes in the brain and blood of mammals after intermittent hypoxia]. / Kompleksy oksida azota s gemoglobinom i paramagnitnye metallofermenty v mozge i krovi mlekopitayushchikh posle kratkovremennoi gipoksii.

AIM: To investigate an effect of hypoxia on the formation of nitric oxide (NO) in the brain and blood of rats and an influence of L-NNA, the NO-synthase inhibitor, and sodium nitrite on NO generation in separate and simultaneous introduction of these compounds in the animal body. MATERIAL AND METHODS: Experiments were conducted on 42 rats of Krushinsky-Molodkina (K-M) line without adaptation to hypoxia and short-term adaptation to hypobaric hypoxia. Animals were intraperitoneally injected with sodium nitrite (0.5 mg/100 g) and the non-specific inhibitor of NO-synthase L-NNA (2.5 mg/100 g) at different times. Changes in NO content were assessed using electron paramagnetic resonance (EPR) by the intensity of nitrosyl Hb-NO complexes in ERP blood spectra. RESULTS AND CONCLUSION: The production of NO in the brain, compared with that in the blood, was significantly reduced, not only under physiological conditions, but also after the administration of moderate doses of NaNO2. In the short-term hypobaric hypoxia, there was the intensification of the processes of the reduction of NO2- to NO and the formation of nitrosyl heme-NO complexes not only in the blood but also in the mammalian brain.

[The use of hydroxamic acids and sodium nitrate to enhance the antitumor effect of cyclophosphamide].

It has been showed that the introduction of nitrocompounds (as nitic oxide donors) in to the compositions of cyclophosphamide and hydroxamic acids for curing animals having leukemia P-388 increased duration of life by 290%. Thereby 40% of animals have recovered. The therapeutic dose cyclophosphamide have been reduced by 6 times.

[Atorvastatin and oxidative stress in coronary heart disease with obesity].

The aim of the work was to study the role of atorvastatin in the correction of oxidative stress manifestations in patients with coronary heart disease and dyslipidemnia (DLP). It included 122 patients with stable forms of CHD and 20 practically healthy subjects. Plasma lipids and products of lipid peroxidation (dienic conjugates and compounds reacting with 2-thiobarbituric acid), eryhrocyte antioxidative enzymes glutathione peroxidase and superoxide dismutase were determined by standard methods; activity of the ceruloplasmin/transferrin antioxidant system) was measured by electron paramagnetic resonance. The patients underwent 24 hr ECG Holter monitoring. Atorvastatin at a dose of 20 mg/d given during 6 months exerted antioxidative and antiperoxidative effects in 90% of the patients. It normalized parameters of lipid peroxidation and antioxidant protection thereby improving the clinical course of CHD.

[Experimental hemorrhagic stroke: the effect of the peptide preparation cortexin in the formation of Hb-NO-complexes and other blood paramagnetic centers].

Using electronic paramagnetic resonance (EPR), we studied the effect of the peptide cortexin on the content of hemoglobin nitrozyl complexes (Hb-NO-complexes) and other paramagnetic centers (transferrin, methemoglobin) in the blood of rats of Krushynsky-Molodkina line in the experimental hemorrhagic stroke induced by acoustic stress. After the acoustic exposure, the level of Hb-NO-complexes have increased by more than 6 times. The intensity of the EPR signal of the plasma peptide transferrin increased by 1,5 times. The level of blood methemoglobin was also elevated, though not significantly, after the acoustic stress. Cortexin substantially reduces the formation of Hb-NO-complexes and, therefore, the level of nitride oxide while the contents of transferrin and methemoglobin remain intact.

[EPR study of the influence of hypoxia on nitric oxide formation in the blood of Krushinskii-Molodkina rats].

The influence of hypoxia on nitric oxide formation in the blood of Krushinskii-Molodkina rats has been studied by electron paramagnetic resonance. It was found that nitric oxide synthesis in Krushinskii-Molodkina rats is increased compared with that in Wistar rats. A significant enhancement of the EPR signal of Hb-NO complexes in the animal blood was observed after hypoxia simulating the altitude of 5000 m above the sea level, in particular in the presence of sodium nitrite and the NO-synthase inhibitor L-nitroarginine. It was assumed that NO synthesis and nitro-/nitrite- reductase systems are activated under hypoxic conditions.

[Lipid peroxidation and antioxidative protection in patients with coronary heart disease].

Total cholesterol as well as cholesterol of low and high density lipoproteins, lipid peroxidation products (LPP), such as dienic conjugates and compounds reacting with thiobarbituric acid, were measured in a single blood sample from each of the 295 patients with CHD and 20 apparently healthy subjects. FC II and III angina was diagnosed in 142 and 151 CHD patients respectively. Certain samples were used to additionally detect homocysteine, activity of anti-oxidative enzymes (superoxide dismutase and glutathione peroxidase) in erythrocytes and ceruloplasmin/transferrin anti-oxidative system in plasma. Patients with FC III angina had significantly higher LPP levels but lower activity of tissue and plasma anti-oxidative systems than patients with FC II angina or healthy subjects. Patients with stable forms of CHD showed correlation between lipid composition, LPP contents, homocysteine level, and activity of anti-oxidative enzymes.

[Correction of antioxidative state during statin therapy of coronary heart disease with dyslipidemia].

Treatment with simvastatin (vasilip) at a daily dose of 20 mg combined with conventional cardiac therapy was given for 3 months to 132 patients with coronary heart disease and postinfarction cardiosclerosis with dyslipidemia. Activity of tissue and plasma antioxidative enzymes increased in 60% of the patients and decreased in 40%. Treatment with antioxidants 2-ethyl-6-methyl-3-oxypiridine succinate (mexidol) and ubichinon (cudesan QIO) improved antioxidative status of the patients and clinical picture of cardiac pathology.

[Nitric oxide is involved in the protective effects of short-term adaptaion to hypoxia in the course of stress-induced disorders in Krushinsky-Molodkina rats].

A possible involvement of nitric oxide in the protective effect of short-term adaptation of Krushinsky-Molodkina rats to mild hypoxia simulating 5000 m above sea level was studied. Nitric oxide proved to have a considerable protective effect on stress-induced disorders in Krushinsky-Molodkina rats as demonstrated using NO-synthase inhibitors and NO monitoring by electron spin resonance under different experimental conditions.

[The influence of the bioflanoid dicvertin on the antioxidative system ceruloplasmin-transferrin and lipid peroxidation in patients suffering from stable coronary heart disease with dyslipidemia].

Thirty-two patients with coronary heart disease (CHD)--exertional angina and postinfarction cardiosclerosis with dislipidemia--were treated with dicvertin (2,3-dihydro-3,5,7-trihydroxi-2(3,4-dihydroxiphenyl)-4H-1-benzopyran-4-on), a Russian antioxidant, during two months in a day dose of 80 mg in addition to conventional cardial therapy. The therapy resulted in positive changes including improvement of CHD clinical picture and biochemical serum indices, such as a 6% decrease in cholesterol level, a 12% decrease in low-density lipoproteins cholesterol level, and a 14% increase in high-density lipoproteins cholesterol level. The intensity of lipid peroxidation decreased, the levels of diene conjugates and TBA-reactive products lowered by 38% and 40%, respectively. The fibrinogen level lowered by 20%. The antioxidative status of the patients increased.

Effect of mexidol and nitroglycerine on iron-sulfur centers, cytochrome P-450, and nitric oxide formation in liver tissue of experimental animals.

In experiments on mice we studied the effect of individual or combined treatment with mexidol and nitroglycerine on iron-sulfur centers of the mitochondrial respiratory chain, cytochrome P-450 of the endoplasmic reticulum, and nitric oxide formation in the liver tissue. Mexidol had a potent effect on these parameters and protected iron-sulfur centers from oxidation, including that induced by nitroglycerine.

[Effects of mexidol on the antioxidative status of patients suffering from coronary heart disease with dislipidemia].

The subjects of the study were 36 patients suffering from coronary heart disease with exertional angina and postinfarction cardiosclerosis with dislipidemia. The patients were administered mexidol (2-ethyl-6-methyl-3-oxipyridin succinate), a domestically produced antioxidative agent, for 1 month in a dose of 325 mg/day together with conventional cardial therapy. The result was good and included clinical improvements and improvements in biochemical serum parameters: cholesterol level decreased by 10%, the level of low density lipoprotein cholesterol decreased by 25%, high density cholesterol level elevated by 15%. The intensity of lipid peroxidation lowered, which was manifested by decrease of the level of diene conjugates and TBA-reactive products by 27% and 42%, respectively. The patients' antioxidative status increased.

[Interaction of E. coli cells with ascorbic acid and sodium nitrite studied by ESR method]. / Issledovanie metodom EPR vzaimodeistviia kletok E. coli s askorbinovoi kislotoi i nitritom natriia.

Ascorbic acid, an effective modulator and regulator of cell metabolism, was shown to induce the production of nitric oxide in E. coli cells. This process was detected by EPR spectroscopy as the generation of a spectral signal typical of nitrosyl-iron-sulfur centers (Fe-S-NO) under anaerobic conditions. Incubation of E. coli cells in the presence of ascorbic acid under aerobic conditions was shown to be accompanied by sodium nitrite formation. It is suggested that ascorbic acid is capable of supporting the system of energy supply to cells in hypoxia caused by reduced oxygen content or treatment with sodium nitrite.

[Release of iron ions from transferrin under the effect of nitric oxide]. / Vysvobozhdenie ionov zheleza iz transferrina pod deistviem oksida azota.

The dynamics of EPR signals from the iron-transporting blood protein Fe(3+)-transferrine after the administration of sodium nitrite and metronidazole to animals was studied. It was shown that exogenin nitric oxide produced by nitrocompounds resulted in the release of iron from Fe(3+)-transferrine.

[Inhibition of cytochrome P-450 when exposed to nitro-compounds]. / Ingibirovanie tsitokhroma P-450 pod deistviem nitrosoedinenii.

Changes in ESR signals from the active form of cyt P-450 in mouse liver samples after administration of some nitro compounds were studied by the ESR method. It is shown that administration of nitro compounds leads to the formation of nitrosyl cyt P-450-NO complexes and a decrease in the ESR signal from cyt P-450 within the first 1-2 h after administration, indicating the inhibition of enzyme activity. It is assumed the nitro compounds induced inhibition of cyt P-450 in the first hours after administration is responsible for the enhancement by imidazoles of the effect of some chemotherapeutic drugs.

Ferrous-ascorbate complexes as carriers of nitric oxide.

Ferrous-ascorbate is known to form with nitric oxide paramagnetic nitrosyl ferrous-ascorbate complexes, Fe-AA-NO. These complexes yield on EPR signal with g-factor close to 2.02 and an optical absorption spectrum with maxima at 340, 460, and 600 nm. Fe-AA-NO complexes are unstable in the presence of oxygen. Ferrous-ascorbate complexes promote NaNO2 decay resulting in the formation of NO. Nitric oxide is taken up by Fe-AA complexes to form paramagnetic ferrous-ascorbate nitrosyl complexes, Fe-AA-NO. It is suggested that ferrous-ascorbate complexes can play the role of carriers of NO and, perhaps, O2 in the blood plasma. Nitrosyl ferrous-ascorbate complexes can also be the NO containing factor involved in the blood vessel relaxation (endothelium-derived relaxing factor, EDRF).