[Antioxidant properties and membranotropic effect of certain derivatives of 1,4-dihydropyridine].

Interaction of alpha-tocopherol and 1,4-dihydropyridine with endoplasmic reticulum membranes and model systems, human serum albumin and phospholipid bilayer, was studied using the microcalorimetry and fluorescent probes procedures. Dependence of microviscosity changes in the endoplasmic reticulum membranes on the place of antioxidants localization (protein structures or phospholipid phase) was shown. Increase of membrane structuralization under the influence of 1,4-dihydropyridines blocked their antioxidant action in spontaneous and induced lipid peroxidation.

[Antiradical and antioxidant properties of nonsteroidal anti-inflammatory agents--derivatives of pyridinecarboxylic acid].

A number of pyridincarboxylic acid derivatives PV-1-4, 7 and emoxypine preparation antioxidative activity in yolk lipoprotein suspension was studied by a method of Fe(2+)-initiated biochemiluminescence. Lipid peroxidation in suspension was effectively inhibited by the studied compounds in various concentration ranges. PV 1, 3, 4, 7 inhibited lipid peroxidation at the concentrations 100-fold, then those of PV 2 and emoxypine.

[Antiradical activity and membranotropic action of cardio- and vasotropic compounds of varying chemical nature].

Antiradical activity and ability to interaction with phosphatidylcholine bilayer of the physiological active compounds (PhAC), concerning the classes of phenylalkilamines (dobutamine, verapamil), dihydro pyridines (BAY-K-4688, nifedipine), analogues of crown ether (carbicyle, diol) was studied. By means of the method of microcalorimetry and spectrophotometry it was shown the complexing ability PhAC with the phospholipid bilayer of the model membrane. It was stated the simbasity in the changes of the thermal effect of the compounds with the negative inotropic activity during its reaction with phosphatidylcholine bilayer and antiradical activity.

[Antiradical and antioxidant activity of certain membranotropic substances of synthetic and plant origin].

Antiradical and antioxidative activities of dieton, phoridon, niphedipin, phlamicar, mildronat in vitro were studied by spectrophotometer's method with the use of dyfenilpycrilgydrasil and method of pulse voltametry. Also influence of drugs was studied under antioxidative insufficiency (AOI), which had modelled by exclusion of alpha-tocopherol from the animal's ration.

[Interaction of phenolic antioxidants and 1,4-dihydropyridines with membranes of rat liver microsome fractions].

Interaction of phenol type antioxidants and Ca-channel blockers, derivatives of 1,4-dihydropyridines, with rat liver microsomes has been studied in vitro by means of spectrophotometry and fluorescent probes using ANS and polymethine dye 4501 u. Incubation of microsomes in the absorption spectra of the antioxidant results in changes of structure dynamic parametres of microsomal membranes, and in changes of their microviscosity and in surface state modification. The mechanism of microsomal action was different for phenol type antioxidants and for 1,4-dihydropyridines and depended on the radical structure.

[Chromatin-protective action of the biologically active preparation BTK-8L in tetrachloromethane and chlorophos poisoning].

Results obtained from the study of the interaction between the phytosteroid preparation (BTK-8L) and fractionated rat liver nuclear chromatin under conditions of the tetrachloromethane and chlorophos intoxications are described. It is shown that preventive injection of BTK-8L to the animals has a partial protective effect on transcriptionally active and repressed liver chromatin. This preparation interacts with chromatin histone proteins binding with them and changes the nucleoprotein complex structure as a results of which the chromatin fraction components become less accessible to the damaging action of tetrachloromethane and chlorophos.

[Effect of stress on lipid peroxidation and physico-chemical status of endoplasmic reticulum membranes in liver of adult and old rats].

As a result of experiments carried out on adult (6-8 months) and old (24-26 months) male rats of the Wistar line it is established that emotional-pain stress results (in one day) in essential increase in the activity of spontaneous, NADPH--and ascorbate-dependent peroxidation of lipids in the liver microsomes, which is expressed in the old animals rather than in the adult ones. The induced peroxidation of lipid six days after the stress effect remains activated in the adult rats and decreases to the control level in the old ones. Accumulation of lipoperoxidation products in the membrane structure of hepatocytes is accompanied by the changes of physico-chemical parameters of microsomal membranes, microviscosity and surface potential in particular.

[Interaction of a substance based on phytoecdysteroids (BTK-8L) with components of fractionated chromatin from intact rat liver].

Results of the study of interaction of the phytoecdysteroid preparation (BTK-8L) with fractionated rat liver nuclear chromatin were described. It was shown that the interaction resulted in the "loosening" of the histone proteins structure both in active and repressed chromatin. At the same time the reparative DNA synthesis in the repressed fraction was stimulated.

[Genoprotective effect of drugs based on ecdysteroids in poisoning of rats with tetrachloromethane and chlorophos].

Molecular mechanisms of chromatin damage have been investigated during tetrachloromethane and chlorophos intoxication of experimental animals. Introduction of tetrachloromethane to experimental animals induced chromatin degradation causing a partial loss of histone H1-DNA fragmentation and formation of intermolecular bonds: DNA-protein. Intoxication with chlorophos results in repression of a part of genes due to augmented chromatin compactness.

[Antioxidant and antiradical activity of various classes of antioxidants].

Antiradical and antioxidative activities of classic phenolic antioxidants and blockers of Ca(2+)-channel have been studied. K2 rate constants and pI50 concentrations of tested physiologically active substances have been determined. Using the model systems of hepatic microsomal membranes lipoperoxidation it is shown that there is no distinct correlation between the antiradical and antioxidative activities of substances under investigation.

[Interaction of antioxidants with differing chemical structure with a phospholipid bilayer].

Interaction of antioxidant (derivatives of phenol and 1,4-dihydropyridine) with bilayer from lecithin was studied by means of electronic spectroscopy and microcalorimetry. The connection of warm effects and spectral properties was estimated by chemical structure of antioxidants. The effect of physiologically active compounds on the structural and dynamic parameters of the bilayer was determined by means of fluorescent probing.

[Lipid peroxidation and calcium transport in rat liver microsomes after chlorofos poisoning and the effect of atropine and verapamil].

Structural and functional state of rat hepatocytes endoplasmic reticulum membranes intoxicated with chlorofos (0,0-dimethyl-(1-oxy-2,2,21-trichloroethylphosphonate) was studied. It was shown that in case of intoxication a breakage of the membrane Ca(2+)-transport function was accompanied by modification of the membrane phospholipid lipoperoxidation processes and by conformational change of proteins. It is established that prophylactic injection of m-cholinolytic atropine and Ca(2+)-channel antagonist verapamil lead to normalization of processes of ATP-dependent potassium ion transport and lipid peroxidation processes (LPO) in the liver microsomal membranes of intoxicated animals.

[Mechanisms of the genoprotective action of a phytoecdysteroid drug (BTK-8L) in chromatin damage by chlorofos].

Genoprotective effect of preparation BTK-8L from plant steroids at prophylactic injection to experimental animals at chromatin damage by chlorofos was revealed. Antioxidant action of the preparation, being most highly expressed in the transcriptionally active chromatin fraction, is, probably, the most likely mechanism of the action. The realization of this action might be carried out as a result of the direct binding of BTK-8L with the chromatin protein-lipid complex, which was revealed during the analysis of the model systems showing binding of the preparation with chromatin fractions in vitro.

[Mechanisms of genoprotective action of a phytoecdysteroid drug(BTK-8L) in chromatin damage by tetrachloromethane].

Hepatoprotective action of prophylactic injection of aqueous solution of preparation BTK-8L from plant ecdysteroids to experimental animals with the liver damage by tetrachloromethane was revealed. This effect at least partially was connected with the genoprotective action of the given preparation. As a result, normalization of free radical chromatin lipid peroxidation reaction, modified at the intoxication, as well as partial correction of physical and chemical properties of chromatin protein-lipid complex were those molecular mechanisms of genoprotective action of BTK-8L, which were manifested by the influence of the preparation on such indices which characterized the depth structure of the complex as microviscosity and energy transfer from the protein to the lipid probe.

[Effect of cadmium chloride on DNA-, RNA-polymerase activity and lipid peroxidation of chromatin fraction in rat liver].

Introduction of the cadmium chloride water solution to experimental animals induces changes in biochemical parameters which characterize structural and functional activity of transcriptionally active and repressed chromatin fractions. In the intoxicated chromatin-active fraction the DNA/protein ratio increases and DNA-polymerase alpha-activity decreases while in repressed chromatin activity of RNA polymerase I decreases as compared with controls. Change in intensity of lipoperoxidation reactions may underlie the cadmium chloride genotoxicity.

[Characterization of enzymatic activity and structure of vesicles of human erythrocyte membranes].

Enzymatic activity and structural peculiarities of human erythrocyte membranes obtained by different methods, are analyzed in the paper. Our studies have demonstrated different enzymatic activity of the preparations of right side- and inside-out vesicles of human erythrocyte membranes. Fluorescence probes of pyrene and ANS have shown that these membrane preparations have different physical characteristics of lipid and conformational properties of membrane proteins and differ in the composition of their protein-lipid ensembles.

[Structural reorganization and change in the lipid composition of rat liver microsomes in chlorophos poisoning].

The influence of chlorophos on the endoplasmatic reticulum of rat liver has been studied using the methods of gas-liquid chromatography and fluorescence. Experiments have demonstrated an increase of lysophosphatidylethanolamine, total phospholipids, unsaturated fatty acids (C20:4 n6, C18:1 n11, C18:1 n7) and a decrease of phosphatidylserine and phosphatidylethanolamine. Changes in microviscosity and surface charge were also shown.

[Biochemical characterization of fractionated rat liver chromatin in experimental D-hypovitaminosis and after administration of steroidal drugs].

Marked changes in the structural and functional characteristics of liver nuclear chromatin fractions are observed under experimental D-hypovitaminosis, which differ in the degree of transcriptional activity. DNA-polymerase activity and activity of the fraction, enriched with RNA-polymerase I, increases in the active fraction. Free radical LPO reactions are modified in the chromatin fraction with low activity and to the less degree in the active one.

[Cu(2+) complexes as inhibitors of free radical oxidation of lipids].

Cu(2+) complexes of chelate ligands have been studied for their effect on oxidation of rat blood plasma lipids, sphingomyelin, lecithin by the method of chemoluminescence. The studied Cu(2+) complexes have been shown to possess pro-oxidant and antioxidant properties depending on their concentration. Antioxidant activity of alpha-tocopherol, ionol (2,6-di(tert)-butyl-4-methylphenol) and Cu(2+) complexes by the lipid oxidation has been compared.

[Changes in the structure and reactions of lipid peroxidation of liver chromatin as affected by 0,0-dimethyl-0,2,2-dichlorovinylphosphate].

Intoxication of rats by 0,0-dimethyl-0-2,2-dichlorovinylphosphate (DDVPh) leads to marked biochemical changes of transcriptionally active (TACh) and repressed (RCh) liver chromatin fractions. These changes are connected with structural relaxation of the fractions, which is manifested by the increase of intensity of protein self-fluorescence. Free radical nature of these changes was supposed, which was proved by the modification of LPO reactions in the both chromatin fractions under the influence of the pesticide concerned.

[Change in the structural state of fractionated liver chromatin in E vitamin deficiency].

Structural modification of transcriptionally active and repressed rat liver chromatin fractions at antioxidant insufficiency caused by E-avitaminosis, was shown. This modification consisted in the compactization of the first fraction structure and in the relaxation of the second one. Besides, compactization of the active fraction structure was accompanied with the increase of fluidity of the lipid bilayer.

[Analysis of the role of calcium in analgesic action of non-narcotic analgesics and calcium channel blockers].

In the mice hot-plate test we have compared analgesic effect of calcium channel blockers and new non-narcotic analgesic antiinflammatory agent PV-107: verapamil > fenigidin > PV-107. Simultaneously we have shown strong correlation (r - 0.82) between analgesic effect and 45Ca2+ efflux of cardiac membrane in depolarizing media in vitro.

[Molecular mechanisms of damage to fractionated liver chromatin by tetrachloromethane].

Impairing effects of tetrachloromethane on genetic apparatus were shown to consist in its high affinity and binding to transcriptionally active fraction of chromatin and subsequent destruction of DNA. As a result of the impairment the density of the chromatin fraction was increased which expressed as elevated stability to hydrolysis by endogenous nucleases. At the same time, content of single-stranded structures enriched with proteins was increased in the DNA of the transcriptionally active fraction of chromatin.

[Peroxide modification of skeletal muscle sarcoplasmic reticulum in antioxidant deficiency and under the effect of ionol. II. Physico- chemical properties of the sarcoplasmic reticulum membrane].

Physico-chemical parameters of membranes of skeletal muscles' sarcoplasmic reticulum in antioxidant insufficiency, which was modelled by excluding alpha-tocopherol from the animals ration, and after treatment with phenol antioxidant ionol were studied. It was shown that activation of lipid peroxidation in vitamin E insufficiency results in a significant lowering of microviscosity of lipid bilayer membranes of sarcoplasmic reticulum. Using polarography significant changes in membrane protein conformation were revealed, which were characterized by lowering of integrity and by disorganization of protein globules.

[Peroxide modification of skeletal muscle sarcoplasmic reticulum in antioxidant deficiency and under the action of ionol. I. Calcium transport into sarcoplasmic reticulum membranes].

It is shown that in case of antioxidant insufficiency (AOI) activation of NADPH- and ascorbate-dependent lipid peroxidation (LPO) in sarcoplasmic reticulum (SR) of skeletal muscles proceeds 1.7 and 4.1 times faster, respectively.