RADIATION DAMAGE OF THE NERVOUS SYSTEM AND ENDOCANABINOIDS. / RADIATsIINE URAZhENNIa NERVOVOÏ SYSTEMY I ENDOKANABINOÏDY.

The review analyzes the change of the existing paradigm of high radioresistance of the nervous system according tothe results of the study of neuropsychiatric disorders in in the aftermath of the Chornobyl accident in both earlyand remote post-accident period. The participation of the endocannabinoid system in ensuring homeostasis andpathology formation, potential possibilities of using cannabis drugs, agonists and antagonists of endocannabinoidreceptors for the treatment of early and long-term effects of radiation are considered.

The effect of N-stearoylethanolamine on plasma lipid composition in rats with experimental insulin resistance.

A model of insulin resistance (IR), induced by prolonged high fat diet with high content of saturated fats was used to investigate the effect of N-stearoylethanolamine (NSE) on the composition of free fatty acids (FFA), plasma lipoprotein spectrum and content of proinflammatory cytokine TNFα in rats. The results of this work showed a rise in the content of monounsaturated fatty acids (18:1 n-9) and a reduction in the level of polyunsaturated fatty acids (20:4 n-6) in plasma of rats with experimental IR. These findings are accompanied by the increased TNFα production and significant changes in plasma lipoprotein profile of rats with the fat overload. Particularly, a decreased high-density lipoprotein (HDL) cholesterol level and increased low-density (LDL) and very low-density lipoprotein (VLDL) cholesterol level were detected. The NSE administration to obese rats with IR restored the content of mono- and polyunsaturated FFA, increased HDL cholesterol content and reduced LDL cholesterol level. In addition, the IR rats treated with NSE showed normalization in the serum TNFα level. Our results showed the restoration of plasma lipid profile under NSE administration in rats with obesity-induced IR. Considering the fact that plasma lipid composition displays the lipid metabolism in general, the NSE actions may play a significant role in the prevention of IR-associated complications.

[Role of sperm phospholipids in its fertilization ability]. / Znachennia fosfolipidiv spermy u zabezpechenni fertyl'noi spromozhnosty.

The functional role of phospholipids in the processes of maturation and fertilization of mammalian spermatozoa is discussed. It is shown that phospholipids take part in the processing, capacitation and acrosomal reaction of spermatozoa. Changes in the phospholipid composition of spermatozoa of some agricultural animals during deep freezing and thawing is discussed. The protective role of some phospholipids in the process of deep freezing is elucidated. It is shown that the parameters of fertile potential of human gametes depend on the phospholipid composition. It is concluded that phospholipids play an important role in fertile ability of the sperm.

[Phospholipids of human seminal plasma and their role in ensuring fertility]. / Fosfolipidy semynal'noï plazmy liudyny ta ikh rol' zabezpechenni fertyl'noï spromozhnosty.

The phospholipid composition of seminal plasma from health (n = 13) and infertile men (n = 49) was studied. A significant decrease of lyso-phosphatidyl choline and lyso-phosphatidyl serine levels in seminal plasma of men with relative infertility was shown. Two-fold enhancement of phosphatidyl serine in seminal plasma of men with excretory infertility was found. A significant decrease of lyso-phosphatidyl choline in men with associated infertility was determined. An essential decrease of lyso-phosphatidyl serine and lyso-phosphatidyl choline in men with secretory infertility were shown. The level of phospholipids correlated with some morphological and functional characteristics of ejaculate.

[Lipid composition and fertility of human ejaculate]. / Lipidovyi sklad ta fertyl'na spromozhnist' liuds'koho eiakuliatu.

The morpho-functional indexes of ejaculates from 35 healthy and 145 infertile men were studied. The depression of functional sperm activity was found in the majority of infertile men. Phospholipid analysis of whole ejaculates from 12 healthy and 35 infertile subjects was performed. It was shown that inorganic phosphorus of total phospholipids decreased in ejaculates of men with secretory infertility. Lyso-phosphatidyl choline (LPC) was not detected in ejaculates of men with relative infertility. The amount of lyso-phosphatidyl ethanolamine (lyso-PE) and sphingomyelin in whole ejaculates of those patients decreased. The levels of LPC and lyso-PE decreased in ejaculates of persons with associated infertility. The level of phosphatidyl inositol, LPC and PE decreased in ejaculates of men with secretory infertility. The gas-lipid chromatography analysis of fatty acids composition of whole ejaculates of the infertile men showed significant changes in quantity of fatty acids. The quantity of docosahexaenoic acid in ejaculates of infertile men decreased and positively correlated with motility of spermatozoa.

[Change in the lipid status of the erythrocyte membrane in essential hypertension]. / Zminy lipidnoho stanu membran chervonokrivtsiv za esentsiinoï hipertenziï.

The erythrocyte ghosts fatty acid composition of 29 patients with essential hypertension of the II stage were investigated. The significant decrease of some saturated fatty acids as myristic, palmitic and stearic under hypertension was established. Simultaneously the percent of omega-6 arachidonic and docosatrienoic acids substantially increased. At the same time no changes in omega-3 fatty acids were observed. The possible relationship between hypercholesterolemia and erythrocyte membrane fatty acid profile under essential hypertension discussed.

[Phospholipids of human spermatozoa and their role in ensuring fertility]. / Fosfolipidy spermatozoïdiv liudyny ta ïkh rol' u zabezpechenni fertyl'noï spromozhnosty.

The phospholipid composition of spermatozoa in healthy subjects (n = 13) and infertile men (n = 38) was studied. The level of inorganic phosphorus of total phospholipids decreased in spermatozoa of infertile men (relative and excretory infertility). It was found that the phosphatidyl ethanolamine amount in spermatozoa of infertile men fell. The level of phosphatidyl serine had certain tendency to decrease as well. Lyso-phosphatidyl serine was detected in some samples of infertile spermatozoa. Correlation between the amount of spermatozoa, its motility, vitality etc. and content of some phospholipids was found.

[The phospholipid composition of the heart in rats with acute vasopressin-modelled myocardial ischemia]. / Fosfolipidnyi sklad sertsia shchuriv za hostroï ishemiï miokarda, zmodel'ovanoï vazopresynom.

The phospholipid composition of the heart of intact and experimental animals has been studied under conditions of simulated acute myocardium ischemia. It is shown that already at the 10th min the phospholipid composition of the heart ventricles changes expressively. The absolute amount of phosphatidylcholine, phosphatidylserine, diphosphatidylglycerol and phosphatidylglycerol decreases reliably. In this case lysophosphatidylethanolamine which is absent in control rats is identified. The amount of other phospholipids does not vary. Simultaneously the percentage of individual phospholipids varies: the phosphatidylethanolamine level significantly increases against the decrease of phosphatidylcholine and phosphatidylserine. As a result of the study of the amount of acylic and plasmalogenic forms of phospholipids it has been found that the level of the diacylic form of phosphatidylcholine in experimental animals falls. The data obtained testify to a definite participation of phospholipids in the pathogenesis of the acute myocardium ischemia.

[In vitro study of the early membrane effects of C27-steroid hormone ecdysterone, immobilized on the nanodispersed magnetite surface]. / Doslidzhennia in vitro rannikh membrannikh efektiv C27-steroïdnoho hormonu ekdysteronu, immobilizovannoho na poverkhni nanodyspersnoho mahnetytu.

The object of the study was to reveal the existence of receptor interactions of C27-steroid hormone ecdysterone with the surface of various cells (liver and spleen macrophages, thymus and spleen lymphocytes, erythrocytes and hepatocytes from rat organs) in experiments in vitro using ecdysterone immobilized on the nanodispersed iron surface (which did not penetrate the cell during observation) and the model of fast (during 15 s) activation of phospholipid signal system with ecdysterone. The parameters, which are characteristic of cell phospholipid signal system activation, were evaluated (the concentrations of free arachidonic acid, diene conjugates, tromboxane B2 and leukotriene C4) and its alteration in response to free and immobilized ecdysterone introduction in suspensins of intact cells and cells with the surface modified in vivo by pre-injection of antigen (human erythrocytes). Concurrent binding of immbilized ecdysterone with intact rat cells in the presence of free ecdysterone was also investigated. It was established that there are high-affinity ecdysterone-specific binding sites on the plasma membranes of all cells investigated, Kd estimated according to two different methods varied in the region of 10(-8)-10(-7) M. The characteristic features of the changes in parameters characteristic of phospholipid system activation were revealed to be queite similar in intact cells, as well as in cells with modified surfaces, under introduction of free ecdysterone and immobilized ecdysterone, which did not penetrate into cytosole. The data obtained point to the existence of ecdysterone receptors on the surface of cells plasma membranes and are indicative of the membrane effects as mechanisms of the early pregenomic phase of cells activation by ecdysterone.

[Brain lipid composition of the rat with experimental morphine dependence]. / Zminy lipdnoho skladu mozku tvaryn z eksperymental'noiu morfinnoiu zalezhnistiu.

The brain phospholipid content was studied in rats with morphine physical dependence. It was found that level of total lipids, total phospholipids and cholesterol was diminished. The significant decrease of absolute amounts of phosphotidyl serine, phosphotidyl inositol, sphingomyelin and phosphatidyl choline was shown. At the same time the percent relation of individual phospholipids did not change. As the exclusion, the quantity of phosphatidyl ethanolamine plasmalogen lowered in rats with morphine dependence. The percent content of fatty acids 16:0, 18:1 omega 9, 20:1 omega 11, 20:4 omega 6 and 22:5 omega 3 was found to be reduced. At the same time the percent amount of i18:0 and 20:0 was shown to increase. As a result the unsaturation index dramatically diminished. It was also shown that under morphine physical dependence the acyl residues of phosphatidyl choline and phosphatidyl ethanolamine changed. It was concluded that lipids play significant role in the development of morphine physical dependence.

[Endothelial dysfunction in obese hypertensive patients]. / Dysfunktsiia endoteliiu u khvorykh na hipertonichnu khvorobu iz suputnim ozhyrinniam.

A total of 28 patients with stage II hypertensive disease (HD) were examined, their age ranging between 32 to 64 years. Of these, 17 subjects were diagnosed as having had alimentary obesity. The control group comprised 11 subjects with normal level of arterial pressure and body mass. Studied in the above patients were blood serum content of nitrogen oxide by determining levels of its stable metabolites NO2- and NO3- anions. HD patients presenting with normal body weight and those with obesity demonstrated significantly lower blood serum levels of anions NO2- and NO3- as compared to healthy subjects. In HD patients, obesity is accompanied by a more significant reduction in blood serum levels of NO2- and NO3-, which fact might be caused by inhibition of nitratereductase.

[Effects of N-stearoylethanolamine on the emotionality and learning ability of rats].

After administration of endocannabinoid-like compound N-stearoylethanolamine (NSE) at a dose of 0,1 and 5 mg/kg the anxiety level of rats in the elevated plus maze and learning ability of rats in the radial maze were investigated. It was revealed that NSE can change both innate and acquired behavior of rats. It was found that the administration of NSE decreased of anxious behavior in general, although number and duration of grooming were not affected. Administration of NSE at a dose of 5 mg/kg decreases of anxious behavior in rats but also decreases locomotor activity. Higher anxiolytic effect of the substance in the elevated plus maze and growth of learning ability in the radial maze were shown during 7 days' introduction of NSE at a dose of 0,1 mg/kg that administration of this substance at a dose of 5 mg/kg. Administration of NSE at a dose of 0.1 mg/kg significantly reduced the total number of errors in the radial maze compared to the control at the first day of conditioning with food reinforcement. The latent period of 3rd reinforcement's taking in animals in this group was lower on the 1st, 5th (P<0.05) and 6th (P <0.01) days. Nevertheless, it was found no significant differences in the behavior in rats treated with NSE in both doses throughout the study period. Therefore, NSE changes the behavior of rats and contributes to the improvement of cognitive function without negative effects specific to cannabinoid drugs.

The effect of N-stearoylethanolamine on cholesterol content, fatty acid composition and protein carbonylation level in rats with alimentary obesity-induced insulin resistance.

The effect of N-stearoylethanolamine (NSE) on liver free fatty acid composition, cholesterol content and carbonylated protein level in rats with obesity-induced insulin resistance (IR) was studied in the work. The experimental insulin resistance was induced by prolonged high fat diet (58% of energy derived from fat) for 6 months combined with one injection of low-dose (15 mg/kg) of streptozotocin. The lipid assay showed a rise in liver free cholesterol content anda significant reduction in cholesterol esters level. Analyzing liver fatty acid composition, a decrease in polyunsaturated of fatty acid (PUFA) level and an increase in monounsaturated fatty acid (MUFA) content was found. Fatty acid imbalance with high content of MUFA was associated with elevated level ofprotein carbonylation. The NSE administration (50 mg/kg of body weight) for 2 weeks decreased free cholesterol content, increased cholesterol esters level and reduced free oleic fatty acid content in the liver of rats with IR. The effect of NSE on lipid imbalance led to a decrease in protein carbonylation level that may result in improvement of transmembrane protein function under obesity-induced insulin resistance state.

[The effect of N-stearoylethanolamine on liver phospholipid composition of rats with insulin resistance caused by alimentary obesity].

We used alimentary obesity-induced insulin resistance (IR) model in rats to investigate the influence of N-stearoylethanolamine on the content of phospholipids and their fatty acid composition. Our results show that prolonged high-fat diet triggers considerable aberrations in the composition of main phospholipids in the liver and can be one of the causes of IR in rats. In particular, the increase of phosphatidylcholine, phosphatidylethanolamine and significant decrease of other phospholipids: lysophosphatidylcholine, lysophosphatidylethanolamine, sphingomyelin, phosphatidylinositol, phosphatidylserine and diphosphaglicerol were observed. The levels of monounsaturated (erucic, nervonic, oleic) and polyunsaturated (eicosatrienoic, docosatrienoic, arachidonic) fatty acids were increased; meanwhile the content of diunsaturated acids was decreased. The NSE administration (50 mg/kg of body weight) caused restoration of the phospholipids content in the liver of rats with diet-induced IR that highly correlated with the decrease in plasma insulin level and the improvement of insulin sensitivity. Moreover, the effect of NSE was accompanied by the normalization of fatty acids composition of phospholipids that could be related to modulating influence of NSE on the activity of the main fatty acid desaturases. It is known that the imbalance in phospholipid composition of the rat liver causes substantial metabolic alterations that are associated with the development of IR. Accordingly, the compensations of the imbalance by NSE can help to restore insulin sensitivity, inhibit the development of obesity, IR and type 2 diabetes.

[N-stearoylethanolamine effect on the level of 11-hydroxycorticosteroids, cytokines IL-1, IL-6 and TNFalpha in rats with nonspecific inflammation caused by thermal burn of skin].

The mechanisms of anti-inflammatory action of saturated N-acylethanolamine--N-stearoylethanolamine (NSE) were investigated on the rat model of nonspecific inflammation (thermal burns of the skin). The results showed that the NSE application in a form of aqueous suspension (10 mg/ml) on the damaged skin area during 12 days significantly accelerated the healing process of burned wounds. NSE also prevented the increase of 11-hydroxycorticosteroids content in the blood of rats with burns. There was also found a significant decrease of cytokines (IL-1beta, IL-6 and TNFalpha) levels under the NSE action. This way may be one of the mechanisms of NSE anti-inflammatory action.

[Organ-specific antitoxic effects of N-stearoylethanolamine in male mice with Lewis carcinoma under doxorubicin intoxication].

With the introduction of doxorubicin into mice with Lewis carcinoma in the heart and liver tissues and kidney the organ-antitoxic effects of N-stearoilethanolamine (NSE) were found, which depended on its concentration. Administration of doxorubicin to male mice leads to an increase in the level of urea and creatinine, as well as activation of ALT in blood plasma. Introduction of NSE resulted in normalization of these parameters to the level of intact animals. In the heart tissue doxorubicin has multidirectional effects on the activity of antioxidant enzymes, in particular it decreases the activity of catalase and superoxide dismutase activity increases. Introduction of NSE normalizes these two indicators. It was found that tumor growth leads to an increase in the activity of glutathione peroxidase and superoxide dismutase. Introduction of NSE normalizes activity of these enzymes. Doxorubicin causes an increase in catalase activity in the kidney of mice with tumour, NSE prevented the increase in the activity of the above enzyme. The cancer process leads to increased levels of catalase activity in the liver of tumour-bearing mice, the introduction of NSE decreases the enzyme activity.

[The effect of N-stearoylethanolamine on the activity of antioxidant enzymes, content of lipid peroxidation products and nitric oxide in the blood plasma and liver of rats with induced insulin-resistance].

The influence of N-stearoylethanolamine (NSE) on the content of lipid peroxidation products, activity of antioxidant enzymes and the nitric oxide level in the liver and blood plasma of rats with insulin-resistance (IR) state was investigated. IR state was induced in rats by prolonged high-fat diet (58% of energy derived from fat) for 6 months combined with one injection of streptozotocin (15 mg/kg of body weight). The existence of IR state was estimated by results of glucoso-tolerance test and blood plasma insulin content. The level of lipid peroxides products was shown to be higher in the liver of insulin resistant animals as a result of reduced superoxide dismutase and catalase activity, however, glutathione peroxidase activity was increased. The increase of nitric-oxide content in the liver and blood plasma of high-fat diet rats compared with healthy control animals was also observed. The administration of the NSE suspension per os in a dose of 50 mg/kg during 2 weeks to the rats with induced insulin-resistance state contributed to the increase of superoxide dismutase, catalase and glutathione peroxidase activity. In consequence of antioxidant enzymes activation the intensity of POL process was decreased. The NSE administration caused normalization of nitric oxide level, restoring pro-/antioxidant balance in the liver and blood plasma of rats with IR state. In conclusion, the NSE administration to the rats with insulin-resistance state restored pro-/antioxidant balance and enhanced the content of nitric oxide, therefore, improving insulin sensitivity.

[Antitoxic and antioxidant effects of N-stearoylethanolamin in the content of nanocomposite complex with doxorubicin in organs of mice with Lewis carcinoma].

The aim of the study was to evaluate the possibility to reduce the doxorubicin toxic effects by its immobilization with N-stearoylethanolamine (NSE) on nanocarier polyethylene glycol. The studied parameters of the doxorubicin toxicity were: the level of creatinine in the mice blood plasma and activity of alanine aminotransferase and aspartate aminotransferase in the blood plasma of mice. The activity of catalase superoxide dismutase, glutathione peroxidase and intensity of lipid peroxidation was determined in the tissues of the heart, kidneys and liver. Doxorubicin in the content of nanocarrier alone caused an increase of serum creatinine and aspartateaminotrasferase activity in plasma of experimental animals with carcinoma. Nanocomposite which contained doxorubicin and NSE, did not cause an increase of these parameters. It has been shown that the administration of a carrier containing doxorubicin to mice with Lewis lung carcinoma caused the decrease of catalase activity in mice with carcinoma. The combination of NSE and doxorubicin on the carrier led to the normalization of this parameter to the level of intact animals. NSE immobilized on a carrier together with doxorubicin caused a decrease in the activity of superoxide dismutase in the kidney tissue of mice with tumor. The tumor growth caused the increase of the of superoxide dismutase in mice. The administration of a carrier which contained doxorubicin and NSE normalized superoxide dismutase in heart tissue contrary of kidney. The obtained results show the antitoxic and antioxidant effects of N-stearoylethanolamine immobilized in the nanocarrier complex together with doxorubicin.

[Effect of N-stearoylethanolamine(NSE) on activity of angiotensine-converting enzyme in the brain structures and blood plasma of rats with streptozotocine-induced diabetes].

The influence of saturated N-acylethanolamine--N-stearoylethanolamine (NSE) on the activity of angiotensine-converting enzyme (ACE) in the brain structures of rats with streptozotocine-induced diabetes was studied. It was shown that decreased activity of ACE was observed in the hypothalamus, increased--in the anterior pituitary. The NSE suspension administration to rats with experimental diabetes in a dose 50 mg/kg of body weight during 10 days caused a decrease in ACE activity in the anterior pituitary, whereas in the hypothalamus and hippocampus ACE activity did not change significantly. At the same time, introduction of NSE to intact animals led to the reduction of activity of ACE in the hippocampus, anterior pituitary and blood plasma. It is known that the highest amount of ACE in the brain structures is located in the membrane-bound state. Thus, the changes we have found in the activity of ACE in the control rats and in animals with induced diabetes may be related to the ability of NSE to the modulation of cell membranes lipid profile. Changes in the activity of ACE under the action of N-acylethanolamines may be one of the mechanisms for implementation of anti-hypertensive and anti-inflammatory action of these compounds.

[Effect of N-stearoylethanolamine on the DNA fragmentation intensity in tumour and extratumoral tissues of the human adrenal cortex].

The effect of different concentrations of N-stearoylethanolamine (NSE 18:0) on fragmentation of DNA in the tumoural and extratumour tissues of the adrenal glands in vitro was studied. In this work the following types of tissue were investigated: extratumoural tissue from patients with hormonally active tumours, benign tumour tissue (hormonally active and hormonally inactive), tissue of malignant tumours and hyperplasic tissue of the adrenal glands (Itsenko-Cushing disease). It has been established that the NSE increases the intensity of DNA fragmentation only in the tissue of hormonally inactive tumours. Benign hormonally active tumours, malignant tumours and hyperplastic tissue of the adrenal glands were resistant to the NSE. The possible mechanisms of resistance to the drug are discussed.