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Biomedical subjects

O A Azizova

Publications and source records attributed to O A Azizova.

At least 55 records · Page 3Linked to original sources

Blockade of ADP-induced Ca2+-signal and platelet aggregation by lipoxygenase inhibitors.

Stimulation of platelets results in the liberation of arachidonic acid (AA) which is further metabolized via the cyclooxygenase or lipoxygenase (LPG) pathway. We have examined the effect of inhibition of LPG on (i) the ADP-induced increase of cytoplasmic Ca2+ concentration and (ii) platelet aggregation. Lipoxygenase inhibitors, nordigidroguaiaretic acid (NDGA) and BW-755C, both suppressed ADP-induced Ca2+-signals and aggregation in a dose-dependent manner, with an IC50 value of 1 2 microM for NDGA. Qualitatively the same effect was obtained with 4-bromophenylacyl bromide, the inhibitor of phospholipases A2 and C. By contrast, cyclooxygenase inhibitor indomethacin had only a negligible effect on Ca2+-signals and suppressed only the second phase of ADP-induced aggregation. It is concluded that the LPG pathway of AA metabolism in platelets might play a crucial role in ADP-induced Ca2+-signal generation and platelet aggregation.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

Neutrophil superoxide production measurement by means of stable nitroxide radical accumulation detected by ESR.

A new assay for superoxide radicals is based on the interaction of hydroxylamine (1-oxy-2,2,6,6-tetramethyl-4-oxopiperidine) with superoxide, giving rise to a stable nitroxide radical. Working concentration ranges of hydroxylamine and cells are determined. It was shown that the amount of superoxide generated was proportional to the concentration of nitroxide radicals. The sensitivity and specificity of the proposed assay were compared to chemiluminescence and cytochrome-c reduction.

Electron Spin Resonance Spectroscopy↗

Free radical lipid oxidation affects cholesterol transfer between lipoproteins and erythrocytes.

Human erythrocytes were incubated for 5 h at 37 degrees C with lipoproteins (LP), preliminary oxidized to different extent, as assessed by thiobarbituric acid (TBA) test. Cholesterol content in the cells was increased by 12-14% after incubation with low-density lipoproteins (LDL) along with augmentation of order parameter and rotational correlation time of spin-labeled stearic acids incorporated into membranes. If erythrocytes were incubated with oxidized LDL, containing 2.5-4 times more TBA-reactive material than native ones, cellular content of cholesterol was increased by 24-28%. In contrast, high-density lipoproteins (HDL2 and HDL3) removed cholesterol from cell membranes, when incubated with erythrocytes. This was followed by increased fluidity of membrane lipid phase as detected by the spin probe method. Oxidation of HDL2 and HDL3 decreased their ability to accept cholesterol from cell membranes. No detectable accumulation of TBA-reactive material was observed in the samples during the incubation. The antioxidant, butylated hydroxytoluene (BHT), in the concentration of 10(-5) M did not influence the cholesterol transfer between LP and erythrocytes. Hence, the effects of lipid peroxidation (LPO) on the cholesterol transfer seem to result from LP alterations by oxidation rather than from free radical reactions occurring during the incubation. By increasing cholesterol-donating ability of LDL and inhibition of cholesterol-accepting capacity of HDL lipid peroxidation in LP may activate cholesterol accumulation in blood vessel cells and thus contribute to atherosclerosis.

Butylated Hydroxytoluene↗

[Indices of lipid peroxidation and the ceruloplasmin-transferrin antioxidant system in donors].

The blood serum ceruloplasmin, transferrin, malonic dialdehyde, iron and copper levels have been measured in donors. These parameters varied in groups of subjects aged 20-29 and 30-45, no age-associated differences being recorded within both the groups. Certain differences have been revealed between the donors who furnished their blood more or less than 3 times a year. The results of this investigation may be useful in clinical screenings of donors.

Adult↗

[Na+/H+ metabolic activity in the thrombocytes of spontaneously hypertensive rats].

The sodium-proton exchange was determined in platelets of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The platelets were suspended in sodium propionate; the cytoplasmic acidification activated the exchanger and intracellular pH (the increasing) and volume of the platelets (the swelling) were registered. The activity of Na+/H+ exchange was inhibited by isopropyl amiloride. The platelets' volume and the exchange rate constant of SHR were increased on 30-40% as compared with those of WKY.

Animals↗

[The red light of the helium-neon laser reactivates superoxide dismutase].

The effect of low-energy helium-neon laser (HNL) on enzymatic activity, absorbtion spectra and electron paramagnetic resonance (EPR) signals of superoxide dismutase (SOD) from bovine erythrocytes in acid medium were investigated. It was found that incubation during 2 hours at pH 5.9 led to eventually complete inactivation of the enzyme. The subsequent illumination of inactivated SOD by HNL brought about the enzyme reactivation. Both absorption and EPR-spectra were changed after incubation at pH 5.9. These changes may be attributed to protonation of histidine residue in the enzyme active site. After laser irradiation both absorption and EPR spectra were restored to those typical of native enzyme at pH 8.2. In a model system, copper-histidine complex, absorption maximum was shifted from 632-633 nm at pH 5.8 to 639-640 nm at pH 8.5-9.0. The similar long-wave length shift of the maximum was observed after illumination by HNL at pH 5.8. It may be postulated that the photoreactivation of SOD consists essentially in deprotonation of His-61 residue in the enzyme active site and subsequent recovery of imidazole bridge between copper and zinc which had been destroyed at low pH. Since many other enzymes possess similar copper-histidine structures in their active sites, one may expect diverse effects of red (laser) light on the enzyme activity.

Animals↗

[Physicochemical and functional properties of the peripheral blood lymphocytes in ischemic heart disease].

Electron spin resonance techniques was used for the investigation of the structural organization of lymphocyte plasma membranes of healthy donors and IHD patients. We found the increased fluidity of peripheral blood lymphocyte membranes of patients with IHD using 5 doxyl stearic acid spin label. The ordering of the membrane lipids increased proportionally to the increase of cholesterol cell content. This is the important reason for the inhibition of mitogenic cell activity during IHD. Measured by the chlortetracycline-fluorescence alterations in the processes of mitogen-induced Ca+2 redistribution might be one of the mechanisms which mediates the influence of membrane structure changes on the lymphocyte functions.

Calcium↗

[The measurement of the amount of iron (III) complexes with desferal in the perfused rat liver by an EPR method].

Rat liver was perfused by Hank's solution, containing desferal (deferoxamine). It was shown that in perfusion of the liver spectrum EPR a signal (g = 4.3; H = 63 G) appears. This signal belongs to desferal complexes, containing intracellular Fe/3/. Desferal transfer to the liver tissue and further formation of desferal complexes there takes place within first 5-10 min of liver perfusion by solution, containing 0.5 mM of desferal.

Animals↗

[Use of spin probe in the determination of oxygen consumption in human neutrophils].

A quantitative method of the oxygen consumption rate measurement by human blood neutrophils upon their activation is described. This method is based on the spin exchange determination between 3-carbamoyl-2,2,5,5-tetramethyl-3-pyrroline-1-yloxyl spin probe and oxygen molecules from the ESR spectra. Method allows the determination of about 1 micromolar concentrations of oxygen.

Cyclic N-Oxides↗

[Effect of verapamil on the functional status of thrombocytes in patients with ischemic heart disease].

A study of 20 anginal patients demonstrated signs of platelet hyperreactivity: increased platelet aggregation, increased mobilization of Ca2+ from platelet membranes, and increased production of malonic dialdehyde. A short-term treatment with isoptin-120 (360 mg daily) produced a considerable drop in those parameters. It is suggested that the drug's basic effect is due to the inhibition of intracellular calcium redistribution in the platelets of coronary patients.

Adult↗

[Secondary atherosclerotic immunodeficiency].

A study of peripheral and central mechanisms of secondary immunodeficiency in atherosclerotic patients demonstrated altered structural layout of lymphocyte membranes due to cholesterol accumulation in the cells. This was associated with increased membrane viscosity, suppressed mitotic activity and lower cap formation rate as well as changed intracellular calcium redistribution. Thymic ischemia due to occlusion or stenosis of thymus-supplying vessels was shown to promote age-related transformation of thymic tissue. Experimental simulation of thymic ischemia resulted in an abrupt drop of serum thymic factor in the blood of animals and the development of an immunodeficient condition.

Animals↗

[Antioxidant therapy in the complex treatment of late pregnancy toxemia].

Lipid oxidation blood levels, activity of serum antioxidative system and erythrocytic membranes were investigated in the time-course of treatment of 145 pregnant females with nephropathies of various severity. More pronounced improvement of the parameters studied and elimination of late gestosis symptoms were revealed in the treatment with antioxidative preparations, lipostabil and solcoseryl. Regardless of treatment pattern in pregnancies complicated by severe nephropathy there were improvements noted, as a rule, in presence of pharmacological management but after its withdrawal the signs of the diseases relapsed (2-6 days after). Continuation of pregnancy up to the terms when the fetus was expected to be born viable was considered as the main target of the aforementioned treatment.

Actihaemyl↗

Photoreactivation of superoxide dismutase by intensive red (laser) light.

The effects of helium-neon laser (HNL) on activity, absorption spectra, and ESR signals of superoxide dismutase (SOD; E Cul.15.1.1) from bovine erythrocytes in acid medium were investigated. It was found that incubation during 2 hours at pH 5.9 led to inactivation of the enzyme. The subsequent illumination of SOD by HNL brought about the enzyme reactivation. Both absorption and ESR spectra were changed after incubation at pH 5.9 and restored after laser irradiation. In a model system, copper-histidine complex, absorption maximum was shifted from 632-633 nm at pH 5.8 to 639-640 nm at pH 8.5-9.0. The similar shift of the maximum was observed after illumination by HNL at pH 5.8. It may be postulated that the photoreactivation of SOD consists essentially in deprotonation of His-61 residue in the enzyme active site and subsequent recovery of imidasol bridge between copper and zinc which had been destroyed at low pH. Since many other enzymes possess similar histidine-copper structures in their active sites, one may expect diverse effects of red (laser) light on the enzyme activity. Heme-containing enzyme, catalase was also found to be photoreactivated by HNL after inactivation at pH 6.0.

Animals↗

[Relation between the changes in Na+/H+-exchange and cytoplasmic Ca levels in platelet activation].

In experiments on human and rat platelets the changes in cytoplasmic pH (pHi) and Ca2+ concentration (Ca2+) have been studied by the use of fluorescent probes BCECF and quin-2, respectively. Inhibition of Na+/H+ exchange resulted in removal of external Na+ (equimolar substitution by cholin) induced a considerable reduction of Ca2+-signal caused by 10 mMPAF, and a slight decrease in Ca2+-signal elicited by 0.1 mu/ml thrombin. In the control Na+ and Ca2+ containing medium both PAF and thrombin induced first a decrease then an increase of pHi above its original level. The latter phase being much more pronounced in the case of thrombin action. Removal of Ca2+ from the external solution suppressed pHi increase and correspondingly it enhanced initial decrease. Addition of Ni2+ also suppressed stimulus-induced pHi increase. A treatment of platelets by Ca-ionophore A23187 caused a rise of pHi without its initial decrease; in medium without Ca2+ the changes of pHi were inhibited. The results obtained suggest that in platelets there exist a mutual interdependence between Ca2+ influx and change in pHi: Ca2+ influx enhanced the activation of Na+/H+ exchange by agonist; in turn Na+/H+ exchange activation enhances the stimulus-induced Ca2+ influx.

Animals↗

[Lipid peroxidation--the factor promoting cholesterol accumulation in cells in atherogenesis].

The cholesterol transfer between human erythrocytes and main classes of serum lipoproteins (LP) from healthy donors and artery-coronary disease patients was studied (artery-coronary disease is the main manifestation of atherosclerosis). It is shown that low-density lipoproteins (LDL) are capable of transporting cholesterol to erythrocytes, which lack the specific receptors for LDL. The cell cholesterol content in comparison with erythrocytes incubated without LDL was increased by 11.4%. The effect was even higher in case of LDL, isolated from serum of artery-coronary subjects (the cell cholesterol content was increased by 33.8%). High-density lipoproteins (HDL) accept cholesterol from cell membranes. However, cholesterol-accepting properties of HDL from artery-coronary disease patients were suppressed as compared with normal HDL. Both discovered events must promote the cholesterol accumulation in cell membranes in atherosclerosis. As it is shown by the spin probe method, lipid peroxidation (LPO) causes the disturbance of the structural organization of LP and as the consequence of that--the increase of LDL cholesterol-donating ability and the decrease of HDL cholesterol-accepting ability. The greater LDL are oxidized, the more cholesterol they transport to erythrocytes during incubation. The greater is the level of HDL peroxidation, the stronger their cholesterol-accepting function is suppressed. These results suggest that LPO can play an important role in LP modification, the disturbance of their interaction with cell surface and the cholesterol accumulation in cells in atherosclerosis.

Arteriosclerosis↗