[Study of the neuroprotective action of hybrid structures based on fullerene C60].

The neuroprotective action of hybrid structures based on fullerene C60 with attached proline amino acid has been studied. Hybrid structures contained natural antioxidant carnosine or addends with one or two nitrate groups. It has been shown that all studied compounds had antioxidant activity and decreased the concentration of malondialdehyde in homogenates of the rat brain. Compound 1, which contained the antioxidant carnosine, has been found to be the most effective antioxidant. All compounds except IV and V inhibited the activity of monoamine oxidase B, while compounds I-IV increased the activity of monoamine oxidase A. All investigated compounds inhibited glutamate-induced Ca2+ uptake into synaptosomes of the rat brain cortex. Compound III, containing two nitrate groups, has been found to be the most effective inhibitor. This compound caused a significant increase of the currents of AMPA receptors (AMPA, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid).

[Anticonvulsants as bioantioxidants under stress conditions].

The action of heterocyclic amides series (ethosuximide, phenytoin, primidone) on lipid peroxidation and membrane bound monoamine oxidases A and B under stress condition has been studied. The intraperitoneal injection of the drugs resulted in enhancement of SOD, decrease of brain malondialdehyde content and mitochondrial activity of monoamine oxidases A and B.

[The inhibitor of free radical processes decrease of protein biosynthesis in gun short wound tissues and weaken development of the general adaptation syndrome].

The dynamics of total protein biosynthesis and procollagen biosynthesis in skeletal muscle of injury tissues with the antioxidant BHT (dibunol) treatment and with common healing were studied. The obtained date indicate that the AO treatment reduce the rate of biosynthesis both the total proteins and procollagen at the 3th day of healing. Dibunol also considerably reduce the protein biosynthesis in adrenals and brake of corticosteroids biogenesis as measured by ESR-signals intensity of reduced adrenodoxine. AO treatment also reduce the protein biosynthesis in thymus, spleen and bone marrow. The lowering of functional activity of endocrine and immune systems indicate that the AO significantly inhibit the systemic reactions of organism induced by acute wound affect. It was suggested that as "primary mediator" of stress-reaction may be considered lipoperoxide radicals and decay products of lipohydroperoide.

[Inhibition of active transport of calcium ions by PT(IV) and PD(II) metal complexes. Correlation between the process and antimetastatic action of drugs].

Newly synthesized compounds, namely, platinum and palladium metal complexes based on substituted pyridinecarboxylic acids inhibit both active transport of Ca ions and hydrolysis of ATP, catalyzed by sarcoplasmic reticulum Ca(2+)-ATPase. The degree of active transport of Ca ions to vesicles correlated to the inhibition of metastases of experimental melanoma B16 by compounds studied. We suggest that the mechanism responsible for inhibition of metastases by newly synthesized compounds consists in change of normal ratio of extra- and intracellular content of Ca2+ ions that influences platelet aggregation, required for adhesion of metastasizing tumor cells to vascular walls.

[Modulation of reactivity of cyclic adenosine monophosphate phosphodiesterase under the effect of pyridinecarboxylic acid derivatives and Pt(IV) metal complexes on their basis].

The effect of substituted nicotinamides and isonicotinamides and Pt(IV) metal complexes based on the substituted nicotinamides and isonicotinamides on the activity of cAMP phosphodiesterase was studied. Isonicotinamide derivatives are efficient enzyme activators, whereas substituted nicotine amides are inhibitors of enzymatic cAMP phosphodiesterase activity; their inhibitory potency is comparable to that of theophylline used as a reference drug.

[Structural-functional changes in biomembranes during complications of diabetes mellitus and their pharmacological correction]. / Strukturno-funktsional'nye izmeneniia biomembran pri oslozhneniiakh sakharnogo diabeta i ikh farmakologicheskaia korrektsiia.

The decrease of sorbitol dehyidrogenase activity and the increase both of aldoso reductase activity and sorbitol concentration in aorta or eye lens under experimental diabetic angiopathy have been shown. The structural and functional alterations in erythrocytes membranes under angiopathy studied by spin- and luminesoense probes confirm the hypothesis on the major role of membrane pathology processes in the pathogenesis of diabetic mellitus. Pharmacological correction of diabetic angiopathy by glucophag or new antioxidant LBK-78 normalized the studied diversions on the membranes level.

Membranotropic properties of the water soluble amino acid and peptide derivatives of fullerene C60.

The modifying effects of the products of the equimolar addition Of DL-alanine and DL-alanyl-DL-alanine to fullerene C60 on the structure and permeability of the lipid bilayer of phosphatidylcholine liposomes has been studied using the luminescence probe technique. It is shown that these water soluble amino acid and dipeptide derivatives of fullerene (C60-AD) are quenchers of pyrene fluorescence and erythrosine phosphorescence of in both a water solution and liposomes. To study the permeability of the lipid bilayer a procedure based on the triplet probe technique has been developed. It has been found that the C60-AD derivatives under study are able to localize inside the artificial membrane, to penetrate into the liposomes through the lipid bilayer and to perform activated transmembrane transport of bivalent metal ions.

[Protective action of an antioxidant of the 3-hydroxypyridine class on the contractility and electrogenesis of the heart muscle in hypoxia and reoxygenation]. / Zashchitnoe deistvie antioksidantov iz klassa 3-oksipiridinov na sokratimost' i élektrogenez serdechnoi myshtsy pri gipoksii i reoksigenatsii.

The effect of SD-6, a 3-hydroxypyridine antioxidant, on the pattern of variation in contraction intensity, contracture and membrane potentials were assessed in experimental studies on isolated left ventricular papillary muscles of rats, exposed to hypoxia and reoxygenation. The antioxidant considerably limited hypoxic and reperfusion contracture, its efficiency increasing with a concentration reduced to 10(-7) g/ml. Contraction intensity and duration of action potentials, diminished by hypoxia, were only recovered by reoxygenation, if the antioxidant was present. It is assumed that the recovery of action potentials by reoxygenation in the presence of SD-6 may result from normalization of ATP-dependent outgoing current through the kappa channels, activated by ATP deficiency. The antioxidant capacity for levelling diverse durations of action potentials between normal and ischemic areas is evidence of an important contribution of free-radical mechanisms to the development of reoxidation-induced recirculation arrhythmias.

[Correlation of the activity of the key enzymes of glycolysis and respiration in hepatomas with different growth rates]. / Sootnoshenie aktivnosti kliuchevykh fermentov glikoliza i dykhaniia v gepatomakh s razlichnoi skorost'iu rosta.

It is shown that an increase in the activity of glycolysis resulting from the rise of the hepatoma growth rate is accompanied by a decrease in the activity of the pentose-phosphate pathway and respiratory chain. It is supposed that variations in the activity both of different carbohydrate catabolism ways and the respiration with a rise of the hepatoma growth rate reflect changes in the relative content of cells at different phases of the cell cycle.

[Oxidation of anthracycline antibiotics]. / Okislenie antratsiklinovykh antibiotikov.

The quantum-chemical estimation of the highest occupied molecular orbital energy for the aglycons of carminomycin, rubomycin, adriamycin and aclacinomycin A in the neutral and ionized states was performed with a semiempirical method. It was shown that the aglycon ionization amplified the electron donor properties of the antibiotics. On the basis of the difference in the absorption spectra of the neutral and ionized chromophores their ionization constants were determined spectrophotometrically. For comparison of the electron donor properties of the anthracyclines at the physiological pH value the reaction of their oxidation with potassium ferricyanide accompanied by decoloration of the solutions was studied. On the basis of the quantum-chemical and experimental data it was concluded that the electron donor properties amplified as follows: aclacinomycin A less than adriamycin-rubomycin less than carminomycin. At the same time their acute toxicity increased (a decrease in the LD50). Therefore, the toxicity of the anthracycline antibiotics could be also due to formation of the radicals with high reactivity on the monoelectronic oxidation.

[Adenosine cyclic-3',5'-monophosphate phosphodiesterase in hepatomas with different growth rates]. / Fosfodiésteraza tsiklicheskogo adenozin-3',5'-monofosfata v gepatomakh s razlichnoi skorost'iu rosta.

The cAMP phosphodiesterase activity in mouse hepatomas 46, 61 and 22A is established to be lower than in the normal liver. Sensitivity of enzymes to inhibitors in tumours is also lower. Dibutyryl-cAMP inhibits the growth of hepatoma 46 and leads to an increase in the functional activity of tumour cells.

[Paramagnetic metal complexes of iron in the regenerative processes of the liver]. / Paramagnitnye metallokompleksy zheleza v regeneratornykh protsessakh pecheni.

ESR study was carried out of the content of oxidized form of cytochrom P-450 at regenerative processes in the liver. It has been shown that after partial hepatectomia and the effect of cycloheximid in the liver of experimental animals regular gradual changes of the content of the paramagnetic form of cytochrom P-450 are observed, an inverse correlation between these changes and protein biosynthesis being noted.

[Free radical mechanism of action of pyrimido-triazine antibiotics]. / Svobodnoradikal'nye mekhanizmy deistviia pirimidotriazinovykh antibiotikov.

EPR spectra of anion radicals were recorded as a result of chemical or enzymatic reduction at various pH of the pyrimido-triazine antibiotics. These anion radicals easily form superoxide radicals in the presence of oxygen. It is supposed that a higher selectivity of reumycin action is due to difference in the redox potentials of the neutral and ionized antibiotic forms. A possibility of enhance the reumycin potency may involve the pH lowering inside the tumor cells - for example, by glucose injections.

[Transformation and the kinetic cell growth patterns in vitro after exposure to adenovirus SV20 DNA]. / Transformatsiia i kineticheskie zakonomernosti rosta kletok in vitro posle vozdeistviia DNK adenovirusa SV20.

Malignant transformation of the normal rat embryo cells has been obtained by monkey adenovirus SV-20 and its DNA. The appearance of the transformed colonies with a multi-layer cell growth was observed at the 28th day. The influence of the growth medium pH on the process of cell transformation has been studied. The kinetic regularities of normal and transformed cells growth were investigated by a cloning assay.

[Biochemical and cytokinetic patterns in the growth of a transplanted pigmented melanoma]. / Biokhimicheskie i tsitokineticheskie zakonomernosti rosta perevivaemoi pigmentnoi melanomy.

Under study were biochemical and cytokinetic patterns of the pigmented melanoma growth in mice. The data obtained allows a conclusion that there is a relationship between the process of melanogenesis and proliferative activity of the tumor tissue. A delayed tumor growth beyond the peak point due to the reduced proliferative pool and increased cell losses is accompanied with a fall in the activity of the key enzyme of melanogenesis and the reduced level of melanoproteids.