[Effect of N-stearoylethanolamine on free amino acid levels in rat plasma and liver with burn].

The effect of the endocannabinoid congener N-stearoylethanolamine (NSE) on the content of plasma and liver free amino acids in burned rats was studied. The animals after the thermal burn of the skin received per os during 7 days the water suspension of NSE in the doze 10 mg/kg of body weight. In the other group of rats the suspension was applied on the wound (the concentration of NSE was 10 mg/ml). In experimental animals the total amount of free amino acids in plasma decreased after burn while the total amount of free amino acids in liver significantly increased. In burn animals the ratio of plasma and liver Phe/Tyr and Gly/Val was found to be augmented while the Fischer ratio (Ile+Leu+Val/Phe+Tyr) diminished compared with intact rats. It was shown for the first time that NSE caused normalization of the concentration of some free amino acids and of Phe/Tyr, Gly/Val ratios, and the Fischer ratio in blood plasma and liver of rats with the burn injury. Altogether, these data demonstrate that NSE possesses adaptogenic properties, and is involved in the organism response to a burn. These findings suggest possibility of NSE usage for burn treatment.

[Protective effect of N-stearoylethanolamine in acute alcohol intoxication in rats].

The influence of N-stearoylethanolamine on the nitric oxide system, the state of lipid peroxidation, antioxidant enzyme activity, content of phospholipids and fatty acids were studied under the acute ethanol intoxication (2.5 g/kg) in rats. The results of investigations show that acute ethanol intoxication caused abnormalities of the oxidative homeostasis accompanied by the accumulation of thiobarbituric acid reactive substances (TBARS). High catalase and glutathione peroxidase activity was also shown. The altered content of total and individual fatty acids of phospholipids in the rat liver tissue was found. The content of saturated fatty acids (palmitic, stearic) increased and amount of unsaturated (palmitoleic, oleic, linolenic) acids decreased under acute ethanol intoxication. The changes of nitric oxide content was found in the brain, plasma and red blood cells. N-stearoylethanolamine (NSE) in a dose of 50 mg/kg of body weight shows the pronounced antioxidative and hepatoprotective properties under these conditions. It was found that the preliminary NSE administration to rats inhibited accumulation of TBARS and caused a simultaneous increase of antioxidant enzyme activity. The NSE administration modulated also the content of total and individual fatty acids of phospholipids and the amount of nitric oxide in pathologically altered tissues. These results suggested that NSE protected the structural integrity and functional ability of cell membranes under the acute ethanol intoxication.

[Anti-inflammatory effect of N-stearoylethanolamine in experimental burn injury in rats].

The biochemical mechanisms of anti-inflammatory effect of endocannabinoid congener N-stearoylethanolamine (NSE) was studied on the model of experimental burn in rats. The animals after the thermal burn of the skin received per os during 7 days the water suspension of NSE in a doze 10 mg/kg of body weight. In the other groups of rats the suspension was applied to the wound (the concentration of NSE was 10 mg/ml). It was shown for the first time that NSE accelerated the process of burn wound healing by the inhibition of proinflammatory cytokines (TNFalpha, IL-6) production. NSE caused the normalization of the iNOS and cNOS activity and of nitrite content in plasma, erythrocytes, liver and spleen of rats. NSE also modified the antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) activity and diminished the level of lipid peroxidation. The discovered anti-inflammatory NSE properties suggest the possibility of its usage for burn treatment.

[Cardioprotective effect of N-stearoylethanolamine under the anaphylactic shock in guinea pigs].

It was shown for the first time that endogenous cannabimimetic compound N-stearoylethanolamine (NSE) administered at the dose 65 mg/kg of body weight during two weeks before anaphylaxis had cardioprotective properties on the model of anaphylactic shock in the guinea pigs. NSE reliably normalized the content of histamine and nitric oxide, decreased the activity both inducible and constitutive NO-synthases, prevented accumulation of thiobarbituric acid reactive substances (TBARS) and normalized the activity of catalase, superoxide dismutase and glutathione peroxidase in cardiomyocytes of animals under anaphylaxis. About of 70% of the NSE-treated animals survived under the anaphylactic shock. The present work indicates that NSE may influence the allergic reaction of immediate type and can possibly be used for design of a new type of antiallergic preparations and cardioprotective preparations as well.

[Immunosuppressive characteristics of N-stearoylethanolamine a stable compound with cannabimimetic activity].

Results of investigation of biochemical mechanisms of N-stearoylethanolamine (NSE) influence on the processes of allergic responses of immediate and delayed type (anaphylactic shock in guinea pigs and contact hypersensitivity to 2,4-dinitrochlorobenzene in mice) are presented in the paper. NSE was given per os during two weeks. It was found that in anaphylactic animals, NSE prevented the growth of histamine levels in the heart, kidneys and spleen, suppressed NO2(-) level increase in these organs and promoted its normalization. At the same time NSE prevented the decrease of the level of stable metabolite of nitrogen oxide - nitrite-anion (NO2(-)) in the liver and to a lesser degree in the lungs, and also decreased the activity both inducible and constitutive NO-synthases. NSE normalized the content of TBA-reactive products in the lungs and decreased it in the heart, diminished the decline of activity of glutathione peroxidase, catalase and superoxide dismutase. Effects of NSE depended on its daily dose. About 70% of animals which received NSE in a dose 65 mg/kg of body weight had no fatal outcome after the induction of anaphylactic shock. NSE suppressed the delayed type hypersensitivity response and normalized NO2(-) content in the blood plasma of mice but only at the dose of 50 mg/kg of weight. In the thymus of sensitized mice NSE diminished the content of NO2(-). Thus, though NSE has no affinity for specific CB receptors, in other words, it is not a typical endocannabinoid, its ability to influence the immediate and delayed type allergic reactions opens a perspective for creation of new medications which differ principally from existing pharmacological drugs with anti-allergic and immunosuppressive properties.

[Effect of N-stearoylethanolamine on the lipid peroxidation process and lipid composition of the rat liver in acute morphine intoxication].

The effect of N-stearoylethanolamine (NSE) on the lipid peroxidation process, antioxidant enzymes activity, phospholipid and fatty acid content in the rat liver tissues under acute morphine administration was studied. It was shown that morphine administration (30 mg/kg of body weight) caused an increase of the amount of thiobarbituric acid reactive substances (TBARS), alteration of antioxidant enzymes activity, decrease the protein level, quantity of total lipids and phospholipids, phosphatidylcholine, cholesterol esters; altered the content of some individual fatty acids. NSE administration (50 mg/kg of body weight) promoted normalization of the antioxidant enzymes activity and prevented the TBARS accumulation and decreased the total lipid and phospholipid quantity, increased the content of free and total cholesterol, corrected the level of free and individual fatty acids. It was assumed that NSE possessed antioxidative, membranoprotective and adaptive properties.

[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.

[Biochemical characterization of fractionated rat liver chromatin in experimental D-hypovitaminosis and after administration of steroidal drugs]. / Biokhimicheskie kharakteristiki fraktsionirovannogo khromatina pecheni krys v usloviiakh éksperimental'nogo D-gipovitaminoza i pri vvedenii preparatov steroidov.

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. Disturbances of chromatine structural properties are caused with the change in the protein and lipid components of chromatin. Administration of ecdysterone preparations (separately and together with vitamin D3) has a partial corrective effect on structural and functional organization of nuclear chromatine. At the action of ecdysterone normalization of LPO reactions modified by pathological changes is observed in the chromatin fraction with low activity and to the less degree in the active one. This kind of influence corrects to the less degree chromatin functional activity and quantitative and qualitative modifications of its protein component. Simultaneous influence of ecdysterone and vitamin D3 leads to the partial normalization of the biochemical indices studied (except for those which characterize LPO reactions) mainly in the active chromatin fraction.

[Ecdysterone induces the activity of multiple forms of acid phosphatase and malate dehydrogenase in fat bodies of Anterahea pernyi pupae]. / Ekdisteron indutsirue aktivnost' monzhestvennykh form kisloi fosfatazy i malatdegidrogenazy zhirovogo tela kukolok dubovogo shelkopriada.

The method of electrophoresis in PAAG has been used to study activity of multiple forms of acid phosphatase and malate dehydrogenase of the fat body of Anterahea pernyi pupae in norm and affected by ecdysterone. It is shown that an increase of total activity of acid phosphatase and malate dehydrogenase with administration of a steroid hormone is promoted by growth of activity of certain inducible multiple forms of the studied enzymes. Ecdysterone injection considerably elevates activity of the most electrophoretically mobile form of acid phosphatase and provokes new formation of malate dehydrogenase form. Ecdysterone-induced increase of activity of the studied enzyme forms in the fat body of Anterahea pernyi pupae is blocked by actinomycin D, an inhibitor of transcriptional processes, and by puromycin, a translation inhibitor. These data permit concluding that an increase in activity of the mentioned forms of enzymes observed with hormonal induction is a result of their synthesis de novo and is mediated by the DNA-dependent RNA-synthesis.

[Composition and physical structure of atherogenic lipoproteins in ischemic heart disease]. / Osobennosti sostava i fizicheskoi struktury aterogennykh lipoproteinov pri ishemicheskoi bolezni serdtsa.

The results of comparative studies in atherogenic lipoproteins of blood plasma under heart ischemic disease (HID) which is accompanied by hypercholesterinemia or proceeds without disturbances in the lipid metabolism, evidence for considerable differences in the composition and physical structure of very low-density lipoproteins (VIDL) and low-density ones (LDP) under the investigated states. The decrease in the surface charge density and in sizes of VLDL, as compared to normal, which are least expressed at HID and an increase in the surface charge density with certain increase of LDL radii under this pathologic state are revealed.