[The Antioxidant and Geroprotective Properties of an Extract of Mountain Ash (Sorbus aucuparia L.) Fruits].

Plant polyphenols are characterized by a wide range of biological activities, including antioxidant properties, and have a high geroprotective potential. The purpose of this work was to investigate the effect of the extract of rowan berries (Sorbus aucuparia L.) on the lifespan and stress resistance of Drosophila melanogaster with the identification of possible mechanisms of its biological activity. It has been established that an ethanol extract of S. aucuparia berries, the main components of which are rutin and cyanidin-3-rutinoside, has a pronounced antioxidant activity in vitro. At the same time, treatment with rowan berry extract increased the resistance of D. melanogaster males to starvation, but reduced resistance to hyperthermia. In females, the extract reduced resistance to oxidative stress but increased resistance to hyperthermia. The effects of rowan berry extract on longevity depended both on its concentration and on the sex of fruit flies. In response to treatment with rowan berry extract, D. melanogaster males and females showed slight differences in the background level of expression of cellular stress response genes, including heat shock genes (hsp27, hsp68, and hsp83), oxidative stress resistance genes (hif1, nrf2, and sod1), circadian rhythm genes (clk and per), and the longevity gene sirt1, which may explain the differences in the observed effects.

Formation of gallic acid layer on γ-AlOOH nanoparticles surface and their antioxidant and membrane-protective activity.

In the reported study we prepared gallic acid modified γ-AlOOH nanoparticles. We proposed mechanism of phenolic compounds binding on the alumina, suggesting covalent and electrostatic interactions. Most of the properties of alumina nanoparticles (NPs) are unchanged, but there is partial reduction of surface charge. Prepared samples are colloidally stable hydrosols. It allowed us to perform biological studies on cellular and non-cellular models, which showed nontoxicity of both pure and hybrid γ-AlOOH nanoparticles. Furthermore, pure alumina NPs exhibit antioxidant properties, which are enhanced after gallic acid immobilization on their surface. Also, hybrid alumina-gallic acid NPs showed membrane-protective activity.

[Synthesis and membrane protective properties of sulfanylimines based on neomenthane and isobornane thiols].

Synthesis of sulfanylimines based on neomenthane and isobornane thiol was carried out with yields up to 85%. On the model of H2O2- and AAPH-induced hemolysis of blood erythrocytes it was found that the sulfenimines have membrane protective and antioxidant activities and inhibit the accumulation of secondary products of lipid peroxidation and oxidation of hemoglobin.

[Some aspects of structural alterations of erythrocyte membranes under the effect of uranyl chloride at low concentrations].

The influence of nanomolar concentrations of the uranyl ion on the parameters of some membrane structures of rodent erythrocytes (laboratory mice and tundra voles--classical objects of radioecological monitoring) was investigated in vitro. A high sensitivity of the tundra vole red blood cells to the uranyl influence was shown. This fact may be determined by the cross-species difference in the membrane structures of erythrocytes--the low sphingomyelin content in tundra voles. Investigation into the phospholipid composition of the erythrocytes incubated in vitro with uranyl ions demonstrates the absence of the membrane lipid component reactions "typical" for the cells circulating in blood and also the changes pointing to the initial stages of eryptosis. Latent alterations in the membrane structure of red blood cells of both species induced by a short time contact with uranyl ions were confirmed by the increase in their sensitivity to nonionic detergent Triton X-100 and indicate the changes in orderliness of the membrane lipid phase.

[Role of the tissue antioxidant status in response to chronic irradiation of mice during early ontogenesis].

The response of the liver and blood erythrocyte lipids to the low intensity chronic γ-irradiation action of mice at the dose of 8 cGy during early ontogenesis immediately and 7 months after irradiation is studied. The maintainance of the changed structural state of the lipid component in liver and especially blood erythrocytes which are characterized by a lower antioxidant status compared with the liver lipids is revealed during a long time after the cessation of irradiation. This confirms the possibility of using blood erythrocyte lipids as a perspective model for the estimation of the effects of the weak impact of unfavorable factors on the organism.

[The influence of uranyl in nanomolar concentrations on erythrocyte sensitivity (in vitro) to factors inducing acute oxidative stress].

The influence of nanomolar concentrations of UO2Cl2 on the erythrocyte sensitivity (in vitro) to the factors inducing acute oxidative stress was investigated. It was shown that even a short-run exposure of uranyl ions resulted in the changes of the physico-chemical properties of the membrane. It can affectnot only the survival of cells but significantly modify their reaction on the effect of damaging factors, particularly on the impact of oxidative stress inductors. The character of modification depends on a radical source and results from the mechanisms of their effects on the cell and the ability of uranyl to catalyze ROS-forming processes. The detailed investigation into the mechanisms of the effect of uranyl ions at low concentration on cells is required.

[Antioxidant properties of conjugates of polyethylene glycols, having a terpenophenolic fragments].

A series of water-soluble conjugates has been synthesized from polyethylene glycols of various lengths and 4-bromomethyl-2,6-diisobornylphenol. Evaluation of membrane protective and antioxidant activity of synthesized products on the model of H2O2-induced hemolysis of blood erythrocytes showed that conjugates have considerable antioxidant activity. A significant membrane protective effect was showed in conjugates with 0.2 and 0.8 mass. % of 2,6-diisobornyl-4-methylene fragments.

[Membrane protective properties of diastereomers of methylpheophorbide a 13(2)-n-n-octyl-N-(2-hydroxy-3-isobornyl-5-methylbenzyl)amide].

Two diastereomers of methylpheophorbide a 13(2)-N-n-octyl-N-(2-hydroxy-3-isobornyl-5-methylbenzyl)amide were obtained from (+)- and (-)-enantiomers of 2-isobornyl-4-methylphenol. Evaluation of membrane protective and antioxidant activity of individual diastereomers on the model of H2O2-induced hemolysis of blood erythrocytes showed that the stereochemistry of isobornyl substituent in the synthesized conjugates has no effect on their biological activity.

[The blood erythrocyte lipid composition of mice exposed to the chronic radiation action at low doses during the early stages of ontogeny].

The comparative analysis of the blood erythrocyte lipid composition of the laboratory mice (males and females) after exposure to the chronic radiation action at the dose of 8 cGy during the early stages of the ontogeny was performed within the early and remote periods after irradiation. This action is shown to cause the marked effect both on the quantitative changes in the lipid composition and the structural state of the blood erythrocyte lipid component as follows from the numerous disturbances of the correlation interrelations between parameters of the lipid composition which are due to the structural state of the erythrocyte membrane. The most substantial changes in the blood erythrocyte lipid composition were detected for males within the remote period after the exposure, which provides evidence in favor of the disorder in the hemopoiesis process. The data obtained allow us to suggest that the erythrocyte membrane viscosity under the chronic low intensity irradiation is supported by the balance maintenance between the relative content of the phospholipid lysoforms and the molar ratio of the [sterols]/[phospholipids].

[Synthesis of novel terpenophenol-chlorin conjugates and evaluation of their membranotropic and membrane protective properties].

A series of terpenophenol-chlorin conjugates where terpenophenolic fragment has amide bond with macrocycle of methylpheophorbide a, formed by amidation of 13(2)-ester group were obtained by interaction of methylpheophorbide a and ortho-aminomethyl derivatives of 2-isobornyl-4-methylphenol. The substances investigated ability to interact with the cell membrane was shown in blood erythrocytes surface structure with scanning electron microscope. The conjugates studied were established to have antioxidant and membrane protective properties resulted from inhibiting H2O2-induced erythrocytes hemolysis and decrease of lipid peroxidation secondary product accumulation.

[Surface active properties of isobornylphenols in systems with different degrees of complexity].

Interrelations between the structure of the semi-synthetic phenolic antioxidants -- isobornylphenols and their surface active properties were studied in the chemical (the lecithin aggregation in hexane) and biological (the incubation with the blood erythrocytes) model systems. It has been shown that all studied compounds are able to affect the lecithin aggregation in hexane: the share of the main fraction of the L micelles decreases with increasing the share of particles of greater size. The effect substantially depends on hindered OH group and the presence of the intramolecular hydrogen bond in molecule. The cytotoxic properties of isobornylphenols (the concentration is 100 M) are predominantly due to the molecule structure. The interrelation between the aggregate size of the main fraction of L in the presence of the studied compounds and the discocyte share during mice blood erythrocyte incubation in their presence for 4 h is revealed. Thus, this provides the possibility to assume that the ability of the different biological active substances to affect the lecithin aggregation in non-polar solvent could be used as a model system for the initial assessment of their surface active properties.

[Comparative analysis of phospholipid composition in erythrocytes of mouse-like rodents of different species].

Comparative analysis of phospholipid quantitative composition of blood erythrocytes has been performed in white (laboratory mice and rats) and wild (tundra voles) mouse-like rodents. A non-characteristic of mammals low relative content of sphingomyelin is revealed in erythrocyte phospholipids in tundra voles. A hypothesis is put forward that the unique composition of erythrocyte lipids is a peculiar evolutionary developed strategy of adaptation aimed at survival under condition of constant circulation of agents of leptospirosis in populations of this species.

[Participation of the lipid peroxidation processes in the adaptation mechanism of Muridae like rodents to the radioactive contamination of the Chernobyl NPP zone].

Results of the comparative analysis of the complex investigation of rodent population state caught at areas with different levels of contamination in the accident zone of the Chernobyl NPP during 1986-1993 and 2007, at areas with a practically normal radiation background in the neighborhood of the Kiev City in 1993 and at areas with the normal and increased radiation background in Ukhta region of Komi Republic in 1993-2008 are presented. It is shown that the absence of the linear dependence in changes of the lipid peroxidation (LPO) regulatory system parameters in rodent tissues on the dose of the external gamma-radiation at areas of their trap persists for a long time. Different ability to normalization of the studied indices and nonlinearity of their dose dependences allow us to suggest that changes of the scale and direction of interrelations between the reciprocal parameters of the LPO regulatory system in norm in tissues of rodents which were caught in the accident zone and at areas with an increased radiation background should be the information signal determining selection of the strategy of adaptation to the chronic radiation factor action.

[Resolution of racemic ortho-isobornylphenol into enantiomers and evaluation of their antioxidant activity].

The resolution of the racemic ortho-isobornylphenol into enantiomers via diastereomeric camphanates was carried out. The absolute configuration ofchiral centers of synthesized compounds was established by the single crystal X-ray diffraction method. Antioxidant activity and membrane protective properties of individual enantiomers were studied on the model of H2O2-induced hemolysis of red blood cells.

[Characteristics of erythrocyte lipids in blood of tundra voles (Microtus oeconomus Pall.) inhabiting areas with increased natural radioactivity].

Interrelations between the lipid characteristics of the blood erythrocytes and 226Ra accumulation in the body of tundra voles (Microtus oeconomus Pall.) inhabiting areas with different levels of the radiation background were investigated. It is shown that the ratio of the phospholipid (PL) fractions which cause the blood erythrocyte structure depends on the phase of the population cycle, as well as on the sex and age of tundra voles. The statistically significant interrelation between lysoforms and the sphingomielin content has been revealed in the blood erythrocyte PL of tundra voles; its scale somewhat differs for the animals from the reference and Ra areas. The peroxide concentration in the blood erythrocyte lipids of tundra voles from the Ra area exceeded the control values in all mature groups of the animals trapped at the depression phase of the population density. The 226Ra content in the bodies of the tundra voles which were trapped in the Ra area at the increased phase of the population cycle is for certain higher than that for the animals from the reference area. Interrelations between the lipid peroxidation parameters in the blood erythrocytes and the body 226Ra content for separate sex-age groups of tundra voles have been revealed.

[Action of the radioactive environment contamination on the age changes of the lipid peroxidation state in the rodent tissues].

Influence of the environment radioactive contamination on the age changes of the lipid peroxidation state in the Microtus oeconomus tissues (rodents caught in the Komi Republic areas and in the Chernobyl accident zone) was studied. The data show that action extent depends on the external y-radiation level in the trapping areas, the animal sex and the supply of the tissue lipids by antioxidants.

[Correlation of phospholipid composition and physicochemical characteristics of lipids in tissues of the root vole Microtus oeconomus of different ages].

There was performed a comparative analysis of phospholipids and of lipid physicochemical characteristics in spleen, blood erythrocytes, and liver of the root voles caught in the natural environmental habitation at different phases of the population cycle, as well as of the animals born and raised throughout the entire life in vivarium, depending on the animals' sex and age. The age-related changes in the phospholipid composition have been established to correlate with lipid physicochemical characteristics, while the scale and direction of the changes depend on the tissue functional role, the initial level of the antioxidative activity (AOA) of its lipids, and sex of the animals. In the process of the organism aging, parameters of the system of regulation of lipid peroxidation change not unidirectionally; in group of animals of the same age, individuals with different biochemical characteristics can be present. Under natural conditions of habitation the degree of expression of age-related changes is modified by populational factors.

[Phospholipid composition of blood erythrocytes of tundra voles (Microtus oeconomus pall.) inhabiting under different radioecological conditions].

Phospholipid composition has been studied in blood erythrocytes of tundra voles Microtus oeconomus inhabiting territories with normal and increased levels of natural radioactivity at different phases of the populational cycle. It has been shown that rearrangement in the lipid component of blood erythrocyte membranes in tundra voles from radioactively polluted areas are associated with intensification of the lipid peroxidation (LPO) processes and are similar to those observed at the organism natural aging. It has been noted that the capability for peroxide oxidation in erythrocyte lipids is one of the most sensitive stages of the LPO processes to action of the low-intensity radiation in the natural habitat of animals. The change of the populational cycle phases, which is accompanied by hormonal rearrangement in the animal organism, produces an essential effect on the degree of expression of the radiation-induced changes of the studied parameters.

[Dependence of response reaction of root voles to low-intensity irradiation on the initial state of the tissue antioxidant system].

There has been studied the response of antioxidant (AO) reaction of the tissue system of the root voles Microtus oeconomus Pall. whose parents belonged to the populations long inhabiting the Republic Komi regions with different degrees of radioactive contamination on an additional radiation action at low doses. Differences have been revealed in the phospholipid content, activities of AO defense, intensities of processes of lipid peroxidation (LPO) in tissues of the vole offspring caught in the control and contaminated regions. It has been revealed that direction and degree of changes in the offspring tissues after the additional action are determined by the parameter value in the non-irradiated animal group. Intensity of the LPO processes in liver and brain was leveled after the long low-intensity irradiation. The obtained data and analysis of literature indicate that at predicting effects of chronic action of low doses of a damaging factor both in experiment and in the natural habitation, it is necessary to take into account initial characteristics of biological objects.

[The age characteristics of lipid peroxidation in tissues from wild rodents].

The comparative analysis of the phospholipid composition and the physics-chemical characteristics of the spleen, blood erythrocytes and liver lipids of wild rodents of different age (Microtus oeconomus Pall.) was carried out. The interrelation between the age changes of the phospholipid composition in spleen and/or the antiperoxide activity and the content of peroxides in lipids was shown. The scale and direct of the age changes of the phospholipid composition depend on the tissue type, basic level of the lipid antioxidative activity and the animal sex. The scale of the age changes of studied parameters is modified by population factors.