[Neuroprotective effect of N-acylethanolamines in chronic morphine dependence. II. Effect on the rat brain fatty acid composition].

The effect of N-acylethanolamines mixture (NAE) with saturated and unsaturated acyl chains on the fatty acid composition of the rat brain under chronic morphine dependence was investigated. Long-term administration of NAE reduced morphine-induced decrease of mono- and polyunsaturated fatty acids in the rat brain crude lipid extract. Furthermore, NAE restored the acyl chain spectrum, especially the content of docosahexaenoic acid in essential phospholipids--phosphatidylcholine and phosphatidylethanolamine. Pharmacological activity of NAE depended on a dose.

[Neuroprotective effect of N-acylethanolamines in chronic morphine dependence. III. Influence on the content of neurotransmitters in the rat brain].

The effect of the mixture of saturated and unsaturated N-acylethanolamines (NAEs) on the functional activity of catecholamine- and serotoninergic systems of the rat brain with experimental morphine dependence was investigated. A significant decrease of dopamine levels was found in the hypothalamus, midbrain and cortex of rats with morphine dependence. The administration of NAEs to rats with morphine dependence in time course dose of 35 mg/kg markedly increased the levels of dopamine in the hypothalamus, middle brain and cortex. Simultaneously the significant decrease of serotonine content was observed in the midbrain and cortex. The results obtained suggest that one of the important aspects of neuroprotective action of NAEs under morphine dependence is the restoration of dopamine content in the brain.

[Neuroprotective effect of N-acylethanolamines in chronic morphine dependence. I. Rat brain phospholipids as a target of their action]. / Neiroprotektornyi efekt N-atsyletanolaminiv za khronichnoï morfinnoï zalezhnosti. I. Fosfolipidy holovnoho mozku shchuriv iak mishen' dlia ïkhn'oï diï.

The influence of saturated and unsaturated N-acylethanolamines (NAEs) mixture on the rat brain lipid composition under the chronic morphine dependence was studied. It was shown that the long-term administration of NAE to rats with experimental morphine dependence restored the morphine-induced alterations of the brain phospholipid composition. This effect can probably be explained by a fatty acyl transfer from NAE to sn-1 position of some brain glycerophospholipids. Another reason of NAE beneficial effect could be due to its antioxidative property, thus providing the remodelling of phospholipid composition. The restoration of the brain essential phospholipids is associated with the decline in morphine consumption in rats with experimental morphine dependence. The mechanism of this phenomenon requires further investigations.

[Effect of exogenous N-stearoylethanolamine on fatty acid composition of individual phospholipids in the isolated rat heart under postischemic reperfusion]. / Vplyv ekzohennoho N-stearoïletanolaminu na zhyrnokyslotnyi sklad indyvidual'nykh fosfolipidiv izol'ovanoho sertsia shchuriv za umov postishemichnoï reperfuziï.

Changes of the individual phospholipid fatty acid composition under the normothermal short-time ischemia with following reperfusion were investigated. Modification of the phospholipid fatty acid (FA) composition under ischemia-reperfusion didn't bear total character and was more manifested in cardiolipin (CL) and phosphatidylethanolamine (PE). The decrease of short chain FA in these phospholipids (more than by 50%) was observed. The amount of unsaturated FA included in CL increased and whole the saturated ones decreased. This caused the rise of the unsaturation index. The selective type of the changes suggested that they had an adaptive character. The addition of the N-stearoilethanolamine (NSE) into the perfusion solution caused a normalization of saturated and unsaturated FA relative amount, as well as of omega-3 and omega-9 FA level in CL. The modification of the FA composition of phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidylinositol (PI) was also found. The quantity of arachidonic acid in PC increased by 26% and the amount of stearinic acid enhanced in PS. The labeled N-([1-(14)C]-palmitoil)-ethanolamine was found in different lipid classes of the rat organs immediately 5 min following intraperitoneal injection. Approximately 1/3 of all incorporated label accumulated in the phospholipid fraction, and more than 50% of the labels were found in CL.

[Effect of stearoylethanolamine on composition of various classes of lipids in rat heart tissue under ischemia-reperfusion]. / Vplyv N-stearoïletanolaminu na rozpodil-lipidiv riznykh klasiv u tkanyni sertsia shchuriv za umov ishemiï-reperfuziï.

The effect N-stearoilethanolamines on lipide classes and their fatty acid composition was studied in the isolated rat heart under ischemia--reperfusion. It was shown that the amount of cholesterol esters increased at ischemia--reperfusion by 4.6 fold. The addition of 10(-7) M, 10(-6) M and 10(-5) M of N-stearoilethanolamines into perfused solution prevented these negative consequences of the myocardium ischemic injury. The addition of N-stearoilethanolamines decreased the quantity oleinic (18:1 omega 9) and free n-6 fatty acids. N-stearoilethanolamine lowered the amount of short chain saturated fatty acids and also polyunsaturated n-6 fatty acids in cholesterol esters. As well the lipide composition of perfused solutions was also investigated.

[Influence of N-palmitoylethanolamine on the phospholipid and fatty acid composition of rat liver in ischemia]. / Vyvchennia vplyvu N-pal'mitoïletanolaminu na sklad fosfolipidiv ta zhyrnykh kyslot pechinky shchuriv za ishemiï

The effect of N-palmitoylethanolamine (NPE, 10(-5) M) on the lipid peroxidation (LPO) processes, phospholipid and fatty acid content in the rat liver at perfusion and ischemia during the liver preservation was estimated. As early as at the 5th min of perfusion by cooled conserving solution "Eurocollins", LPO activation was determined. Simultaneously the content of lysophosphatidylcholine (LPC) and phosphatidylserine increased, the total cholesterol level decreased. The redistribution of saturated and unsaturated fatty acids quantity was detected. The addition of NPE into "Eurocollins" solution reduced the accumulation of malonedialdehyde and LPC, modified the fatty acids content. These effects, evidently, formed the basis of the protective action of NPE on the hepatic tissues under anoxia.

[Changes in myocardial lipid composition during surgery with cold and chemical cardioplegia]. / Zminy lipidnoho skladu miokarda v umovakh khirurhichnoho vtruchannia z vykorystanniam kholodovoï ta khimichnoï kardioplehiï.

The changes of children myocardium lipid composition were studied for the first time during surgical intervention under cold crystalloid cardioplegia. The surgical intervention was performed as a result of congenital heart disease--atrial septal defect. It was shown that the quantity of short chain fatty acids decreased and the amount of long chain fatty acids increased in the content of phospholipid fraction. Simultaneously the amount of linoleic (C18:2 omega 6), of docosahexaenoic (C22:6 omega 3) and of some other fatty acids decreased in the content of cholesterol esthers. The accumulation of free linoleic (C18:2 omega:6), (C18:2 omega:4) and linolenic (C18:3 omega:6) acids was found. Reperfusion caused the additional changes of myocardium lipid composition. The amount of palmitic (C16:0) acid decreased by 30%. The quantity of some other saturated free fatty acids also diminished. Simultaneously the content of free oleic (C18:1 omega 9) also decreased as a consequence of lipid peroxidative processes activation. The ratio of omega 6/omega 3 increased during the few first minutes of reperfusion in the fraction of free fatty acids and cholesterol esthers.

[Erythrocyte membrane fatty acids in ischemic heart disease]. / Zhyrni kysloty membran erytrotsytiv za ishemichnoï khvoroby sertsia.

The erythrocyte ghosts fatty acid composition of 27 patients with coronary artery disease (CAD) and 6 healthy people were investigated. Patients suffering from CAD were divided in two groups. The first group was matched by 18 patients with CAD and essential hypertension (EH) and 9 patients with CAD without EH. Significant decrease of the levels of some saturated fatty acids such as palmitic, stearic and begenic acids in the erythrocyte ghosts of the patients with CAD without EH was established among the major changes of the erythrocyte ghosts fatty acid composition. At the same time the amount, of arachidonic acid increased by 74% and docosahexaenoic acid--by 5.7 times. The content of miristic, palmitic and stearic acids was also diminished in patients with CAD and EH. The percent of arachidonic acid was elevated by 51% and docosatrienic acid--by 94%. It is notable that the quantity of docosahexaenoic acid did not change markedly if copmare to healthy people but was fallen for 5 times if compare to patients with CAD without EH. It was suggested that the lack of adaptive changes in erythrocyte ghosts omega-3 fatty acids of patients with CAD and EH was an important factor which could rise the risk of heart attack development.

[Effect of N-palmitoylethanolamine on phospholipid and fatty acid level in ischemic rat liver under reperfusion]. / Vyvchennia vplyvu N-pal'mitoiletanolaminu na sklad fosfolipidiv ta zhyrnykh kyslot ishemizovanoi pechinky shchuriv za reperfuzii.

The effect of 10(-5) M N-palmitoylethanolamine (NPE) on lipid peroxidation processes, phospholipid and fatty acid content in the ischemic rat liver under reperfusion was estimated. It was shown the significant accumulation of thiobarbituric acid reactive substances (TBARS), the increase of lysophosphatidylethanolamine (LPC), phosphatidylserine, phosphatidylethanolamine, sphingomyelin, general cholesterol content and also the decrease of phosphatidylcholine amount in the ischemic rat liver under reperfusion. Simultaneously the redistribution of saturated and unsaturated fatty acids quantity was detected, that indicates the increasing of membrane rigidity. The addition of NPE into the Eurocollins and Bretshneider's solutions under perfusion and preservation of a donor organ reduced the accumulation of TBARS, LPC, total cholesterol, prevented the changes of cholesterol/phospholipids and saturated/unsaturated fatty acids ratio value in the same experimental conditions. These effects, evidently, formed the basis of the protective action of NPE on the ischemic liver tissues under reperfusion.

[Influence of saturated long-chain N-acylethanolamines on lipid composition and heart contractility of isolated rat heart under ischemia-reperfusion]. / Lipidnyi sklad i skorochuval'na aktyvnist' izol'ovanoho sertsia shchuriv za postishemichnoï reperfuziï ta umov vplyvu nasychenykh dovholantsiuzhkovykh N-atsiletanolaminiv.

The heart contractility and changes of lipid composition of isolated rat heart (n = 26) under total ischemia and ischemia-reperfusion was studied. The effect of N-stearoyl-ethanolamine under these conditions was investigated. N-stearoyl-ethanolamine leads to remodelling of fatty acyl chain composition of myocardial phospholipids: to drastic fall of polyunsaturated fatty acyl chains (18:2w6, 20:3w6, 20:4w6, 22:5w3, 22:5w6, 22:6w3 and 22:6w6) and enhancement of 18:0. This can be caused by N-stearoyl-ethanolamine-induced suppression of polyunsaturated fatty acids synthesis. Naturally occurring minor lipids--N-acyl phosphatidylethanolamine and its derivative N-acylethanolamine were detected in isolated rat heart under ischemia-reperfusion. It is notable that approximately 12% of total N-acylethanolamines were composed by anandamide. Treatment of N-acyl phosphatidylethanolamine by phospholipase D with subsequent fatty acyl chain analysis demonstrates that fatty acid composition of both N-acyl chains of N-acyl phosphatidylethanolamine and free N-acylethanolamine are similar and their main fatty acyl chains are 16:0, 18:0 and 20:4w6. It was shown that exogenous N-stearoyl-ethanolamine did not alter the levels of endogenous N-acyl phosphatidylethanolamine and N-acylethanolamine, but caused the decrease of lyso-phosphatidylcholine and phosphatidylglycerol levels. The rate of heart contractility and heart relaxation was found to increase during the early period of reperfusion. N-stearoyl-ethanolamine prevents this alteration and exerts a negative inotropic effect. It is concluded that membrane protective properties of N-stearoyl-ethanolamine at least partly depend on its ability to inhibit decrease amount of arachidonic and docosahexaenoic acids, to modulate the fatty acyl chains of cardiac phospholipids and to decrease the level of lyso-phosphatidylcholine.

[N-acylethanolamine--a new class of natural adrenotropic modulators]. / N-atsyletanolaminy--novyi klas pryrodnykh adrenotropnykh modulatoriv.

N-acyl-ethanolamines (NAE) belong to the new class of naturally occurring biologically active regulators. Anandamide--a well known representative of NAEs--is an agonist of central (CB1) and peripheral (CB2) cannabinoid receptors. Adrenal cortex contains the CB2 receptor. The aim of present work is to investigate the influence of saturated and polyunsaturated NAEs on the corticosteroid synthesis in adrenal gland in vitro. It was shown that the rat adrenal gland is the main target of N-([1-14C]palmitoyl)ethanolamine incorporation. Saturated NAE enhanced the incorporation of [3H]-cholesterol into the aldosterone by 25% (p < 0.06) and corticosterone by 17% (p < 0.05) of rat adrenal slices in vitro. Mixture of polyunsaturated NAEs containing mainly 18:1w9, 18:2w6, 18:3w3, 20:1w9, 22:1w9 increased the labeling of aldosterone by 70% (p < 0.05) and corticosterone by 20% (p < 0.05). Thus, the saturated NAEs as well as polyunsaturated analogs, act by the similar manner on the corticosteroid synthesis. The fact that saturated NAEs possess poor affinity to CB receptors provides us opportunity to suggest the non-receptor mechanism of NAEs adrenotrophic action. Further we used the purified bovine serum albumin to test the binding kinetic of N-([I14C]palmitoyl)ethanolamine with its hydrophobic domains. It was found that NAEs have high affinity to hydrophobic domains of protein with K = 2.5 x 10(8) M-1. This finding could support the idea of the existence of putative allosteric modulation of regulatory protein function. It was concluded that NAEs exert a stimulatory effect on the corticosteroid synthesis in rat adrenal gland in vitro and this action do not mediated trough cannabinoid receptor.

[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.

[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.

[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.

[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 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.

[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.