[Protective effect of N-stearoylethanolamine in suspension and in nanocomposite complex in the organs of mice with the Lewis carcinoma under doxorubicin intoxication administration].

The antioxidant effects of N-stearoylethanolamine (NSE) in the nanocomplex composition and in suspension are shown on the model of intoxication by doxorubicin in conditions of development of the Lewis carcinoma in the heart, kidneys and liver tissue and in the blood plasma of female mice. The NSE suspension reduces the level of urea in the blood plasma of mice with the Lewis carcinoma, which growth was revealed as a result of introduction of doxorubicin. Under introduction of nanocomplex the amount of urea remains at the level of that in the intact mice. In the blood plasma of mice with the Lewis carcinoma the NSE suspension and nanocomplex reduce activity of aspartate aminotransferase, the basic marker of necrosis of the heart tissue, growth of which was caused by the tumour development. Doxorubicinum increases activity of alanine aminotransferase, the marker of the liver lesion; introduction of NSE in the nanocomplex composition prevents the growth of the enzyme activity. N-stearoylethanolamine, both in the nanocomplex and in suspension, modulates activity of enzymes of antioxidantive protection of the heart, kidney and liver tissue of mice with the Lewis carcinoma.

[Antioxidative effect of the N-stearoylethanolamine in the heart tissue and blood plasma of rats under doxorubicin treatment].

The influence of N-stearoylethanolamine on the alterated antioxidant enzyme activity in the heart tissue and blood plasma of rats under the doxorubicin treatment was investigated. It was shown that doxorubicin administration caused the decrease of antioxidant enzymes activity (superoxide dismutase and glutathione peroxidase) in the heart tissue. Administration of the NSE promoted the partial normalization of these enzymes activity. It was shown that doxorubicin treatment caused the increase of the urea and creatinine level in the blood plasma of experimental animals. The NSE administration normalized the level of the urea and did not affect creatinine level.

[N-stearoylethanolamine inhibits the proliferation of transformed cells and modulates mitochondrial enzyme activity in normal and transformed cells].

The N-stearoylethanolamine (NSE) influence on the proliferation of different cell types and the activity of mitochondrial electron transport enzymes, succinatedehydrogenase (SDG) and glycerophosphate-dehydrogenase (GFDG), in transformed cells under the action of NSE was studied. The incubation of the cells of mouse leukemic lymphocyte cell line L1210 and transformed mouse fibroblasts L929 with NSE caused the inhibition of cell growth and decreased the survival level of cells, but this effect was not associated with apoptotic cell death. It was shown for the first time that NSE addition to the cultural medium decreased the SDG activity and increased the GFDG activity in L929 cells. That leads to the SDG/GFDG imbalance in transformed fibroblasts and affects the cell energy metabolism. The results of the work suggest that N-stearoylethanolamine inhibited the transformed cell proliferation due to modulation of the activity of electron transport enzymes.

[Influence of N-acylethanolamines on embryonic cell culture survival under the effect of irradiation].

The effects of the N-stearoylethanolamine (NSE), N-oleoylethanolamine (OEA) and N-acylethanolamine (NAE) mixture on the cell survival, apoptosis and activity of mitochondrial succinate dehydrogenase (SDG) and glycerophosphate dehydrogenase (GFDG) in embryonic cell culture under normal conditions and irradiation were compared in the work. It was shown, that all investigated NAE were able to modulate the proliferative activity of intact cells as well as irradiation-exposed cells in concentration-depended manner. The most pronounced effect was observed under the NAE mixture action. It was established, that NAE prevented the damage effects of the irradiation and diminished the activation of apoptotic cell death. It was found that NSE and OEA decreased the activity of the SDG (42.3 and 44.14%, accordingly) and the GFDG activity (14.67 and 17.33%, accordingly) in embryonic cell culture, while addition of the NAE mixture decreased SDG activity by 20%, at the same time GFDG activity increased by 20%. Our findings suggested that antiproliferative effects of NAE depended on their influence on mitochondrial functioning.

[N-stearoylethanolamine inhibits growth and metastasis of the Lewis carcinoma and modulates lipid composition of the lung during tumorogenesis in mice].

We investigated the influence of N-stearoylethanolamine (NSE) on tumor growth and metastasis of the lung Lewis carcinoma in mice. The effect of NSE on lipid composition of lung tissue under tumorogenesis was also studied. We demonstrated that NSE inhibited the tumor growth and decreased the volume and quantity of metastases being administered from the fourth day after injection of tumor cells to the last day of experiment and being administrated from the 21th day after injection of tumor cells to the last day of the experiment. The analysis of the lipid composition of the lung tissue showed the decrease of total phospholipid levels and change of the phospholipid spectra under tumor growth. The decreasing of the concentration of phosphatidylcholine, sphyngomyeline, phosphatidylserine and lysophosphatidylcholine in the lung tissue of tumor-bearding mice in comparison with lung of intact animals was observed. It was found that administration of NSE increased the level of lysophosphatidylcholine and decreased the concentration of phosphatidylinositol in investigated tissues. The content of sphingosine was increased in lung tissue of mice fed by NSE in comparison with tumor-bearing mice. The carcinoma development was associated by the significant decreasing of cholesterol level and by the increasing of unsaturated fatty acids in membrane phospholipids. The amount of the tiobarbituric acid (TBA) reactive substances in tumor-bearing mice was elevated. The administration of NSE inhibited the accumulation of TBA reacting compounds.

[The effect of N-stearoylethanolamine on lipid composition of the metastases and conditionally normal lung tissue in mice with Lewis carcinoma].

Influence of NSE on lipid composition of metastases and the neighbouring conditionally normal lung tissue in mice with Lewis carcinoma was investigated. The processes of peroxidation in investigated tissues were also studied. It was shown that under the influence of NSE the high level of antioxidant activity in the metastases was decreased, while in the neighbouring conditionally normal lung tissue the catalase activity was increased. The content of the thiobarbituric acid-reactive substances in comparison with animals which were not fed by NSE was decreased. The development of carcinoma was accompanied by significant decrease of cholesterol level and by the increase of unsaturated fatty acids esterified in membrane phospholipids in both the metastases and the neighbouring conditionally normal lung tissue. An analysis of the phospholipid spectra shows that under tumor growth in investigated tissues the high-level lysophosphatidylcholine (LPC) was observed. The content of phosphatidyl choline (PC), phosphatidyl ethanolamine (PE), phosphatidyl serine (PS) was found to be significantly lower than in the lung of intact animals. It was found that administration of NSE to tumor-bearing mice contributed to the increase of cholesterol level, to the decrease of omega-6/omega-3 ratio polyunsaturated fatty acids of total phospholipids. NSE modulated the phospholipid membrane composition in both the metastases and the neighbouring conditionally normal lung tissue.

Incorporation of labelled N-acylethanolamine (NAE) into rat brain regions in vivo and adaptive properties of saturated NAE under x-ray irradiation.

Regional distribution of exogenous N-palmitoylethanolamine in the rat brain was investigated in the study. Possible protective and adaptive effect of N-stearoylethanolamine under 2 Gy whole-body X-irradiation and changes of brain lipid composition were also studied. It was found that after per os administration to rats N-([9,10-3H]-palmitoyl)-ethanolamine was primarily accumulated in hypothalamus, pituitary and adrenal glands and the label amount in brain was 0.95% of the oral dose. Quantities of palmitic acid in total brain phospholipids and plasmalogen form of phosphatidylcholine were increased; free cholesterol and diacyl form of phosphatidylcholine were decreased in 2 weeks after irradiation. 11-OH-corticosteroid level in the blood of exposed rats was decreased in comparison with control animals. N-stearoylethanolamine pre-treatment prevented from increasing the plasmalogen form of phosphatidylcholine and decreasing its diacyl form and restored 11-OH-corticosteroid level in the blood of irradiated rats. Recovering of brain free cholesterol level was observed when N-stearoylethanolamine was post-treated. So, the accumulation of N-([9,10-3H]-palmitoyl)ethanolamine in brain indicates its penetration through blood-brain barrier and suggests the possible role of saturated N-acylethanolamines in brain functioning, particularly, in stress response regulation of the organism by hypothalamus-pituitary-adrenal system. N-stearoylethanolamine treatment of irradiated rats causes protective effect concerning the of irradiation induced changes in the brain lipid composition and in 11-OH-corticosteroid level and modifies phospholipid fatty acid composition.

[Effect of N-stearoylethanolamine on the level of stable NO metabolites in different pathological conditions which are accompanied by oxidative stress].

The effects of N-stearoylethanolamine (NSE) at the level of stable NO metabolites--NO2- NO3- under different pathological conditions which were accompanied by oxidative stress and NO disbalance were studied. It was found that NSE promoted the increasing of NO metabolites level on the animal models with deficit of NO compared to control and evoked decreasing content of NO2- and NO3- under pathological conditions with NO overproduction. It is suppoused, that NSE effects could be determined, by its ability to modulate the the activity of NO-synthase izoformes.

[Effect of phospholipids containing omega-3 fatty acids on structural changes of microsomal lipids in cell membranes of functionally different cells]. / Vplyv fosfolipidiv, shcho mistiat' omeha-3 zhyrni kysloty, na strukturni zminy lipidiv mikrosom membran klityn, riznykh za funktsiieiu.

As a result of the experimental researches conducted it has been shown that administration of some normal animal marine phospholipids (PL) including in their structure omega-3 polyunsaturated fatty acids (PUFA) provides for quantitative changes of individual PL, fatty acids (FA) content and quantity in general and individual PL of liver, heart, brain and gonads microsomes. While estimating general microsomal PL fraction FA content under the action of PL omega-3 PUFA FA concentration change, unsaturation index (omega 6/omega 3) and relation of arachidonic acid to docosahexenic (AA/DHA) decrease have been identified. The decrease of AA/DHA relationship occurs due to AA and DHA quantitative changes. In the case of AA increase in some tissues there is observed the decrease of docosapentaenic acid and increase of DHA and eucosapentaenic (EPA) acidds. As a result of studying FA content in the individual PL composition it has been identified that certain PL classes characteristic for some tissues respond by changes of some certain FA. The relationship omega 6/omega 3 has been shown as decreasing in phosphatidilcholine (PC) all tissues microsomes (liver, gonads, heart, brain), in phosphatidilethanolamine (PEA) of liver and cardiac microsomes, in phosphatidilserine (PS) this relationship relationship decreases in the liver, brain and heart, for phosphatidilinositole (PI) the changes take place in liver, gonads, brain. Simultaneously, the decrease of AA/DHA relationship in the individual PL decrease of AA and increase of EPA and DHA depend on the tested tissues. The marine phospholipids might be supposed to render their effect on AA metabolism resulting in AA/DHA relationship in PEA and PS relationship displays itself as specific and depends on the tissues functions. The preference of PEA and PS use by certain tissues microsomes could be explained by their membrane protective capability.

[Role of phospholipids in functionally different cell membranes under conditions of antioxidant system disturbance]. / Rol' fosfolipidiv u membranakh funktsional'no riznykh klityn za porushennia antyoksidantovoï systemy.

Vitamin E deficiency in organism leads to microsome membrane phospholipid composition changes, oxidation, superoxide dismutase (SOD) activity decrease, accompanied with the disorders of lung and liver tissues functional state which is connected with regulation of membrane penetration. The negative effect of E-hypovitaminosis more affects the liver than lung, which is caused by their different functional purposes, peculiarities of metabolic processes as well as by the content of biomembrane structural components. Vitamin E protects phospholipids from oxidation, regulates AOS condition, SOD-activity and promotes in such way the tissue functional disturbances correction of the animals tested. New preparation "Calmophyl" is a phospholipid complex from marine organisms with surfactant-kind effect, which displays antioxidative properties and decreases toxic affect of CCl4, corrects functional tissue disorders, regenerates normal activity of enzymes. Preparation of natural phospholipids has been shown to be capable to stabilize cell membranes probably by means of replacing the membrane phospholipid composition and decreasing disturbances in the antioxidative system.