RESUMEN
The purpose of this study was to establish phospholipid composition of the myocardium in patients with ischemic heart disease, and to estimate possible correlation of biochemical parameters with myocardium extrasystolic activity. The patients (n = 28) including 15 patients with ischemic heart disease and 13 patients with secondary atrium septum defect (control group) were studied. During surgical intervention the right atrium myocardium bioptates were taken. Phospholipid metabolism was studied in the myocardium samples. At the eve of surgical intervention a holter monitoring was performed. Deep changes in the myocardium lipid metabolism were found, including accumulation of free and estherified cholesterol, lysophospholipids, and sphingomyeline. An increase of free cholesterol content was accompanied by accumulation of sphingomyeline. This can be an evidence of changes in the constitution of lipid rafts. Extrasystoles, particularly ventricular ones, in patients with ischemic heart disease might depend on accumulation of lysophospholipids as they took place simultaneously with it.
Asunto(s)
Complejos Cardíacos Prematuros/metabolismo , Isquemia Miocárdica/metabolismo , Miocardio/metabolismo , Fosfolípidos/metabolismo , Adulto , Complejos Cardíacos Prematuros/etiología , Complejos Cardíacos Prematuros/fisiopatología , Complejos Cardíacos Prematuros/cirugía , Electrocardiografía Ambulatoria , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/fisiopatología , Isquemia Miocárdica/cirugíaRESUMEN
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.
Asunto(s)
Encéfalo/efectos de los fármacos , Etanolaminas/uso terapéutico , Ácidos Grasos/metabolismo , Dependencia de Morfina/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Animales , Encéfalo/metabolismo , Enfermedad Crónica , Modelos Animales de Enfermedad , Etanolaminas/administración & dosificación , Inyecciones Intraperitoneales , Masculino , Dependencia de Morfina/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Ratas , Ratas WistarRESUMEN
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.
Asunto(s)
Encéfalo/efectos de los fármacos , Etanolaminas/uso terapéutico , Dependencia de Morfina/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Fosfolípidos/metabolismo , Animales , Encéfalo/metabolismo , Enfermedad Crónica , Modelos Animales de Enfermedad , Masculino , Dependencia de Morfina/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
The influence of irradiation and NSE on the microsomal lipid composition of the rat liver and heart was studied. It was shown, that radiation treatment in a dose of 2 Gy had not a significant affect on the heart phospholipid composition, whereas in the liver the amounts of the phosphatidylethnolamine and phosphatidylinositol were increased and the amounts of the phosphatidylcholine and sphyngomieline were decreased. NSE did not impact on these characteristics. The alterations of the plasmalogen/diacyl forms ratio of the PC and PE also took place only in the liver microsome. The analysis of the fatty acids esterified to phospholipids showed similar situation: the fatty acids of the heart microsome less were changed than those of the liver microsome undergo irradiation. The amount of arachidonic acid rise after the adding of NSE to rats. Investigation of the important component of biological membranes--cholesterol and its esters also showed that the liver tissue is more vulnerable to irradiation than the heart. NSE led to insignificant increase of the not esterified cholesterol in the liver. As a result of the present work we may conclude that the liver microsome is more vulnerable than the heart under X-ray radiation and NSE has protective effect in these conditions.
Asunto(s)
Etanolaminas/farmacología , Corazón , Microsomas Hepáticos , Microsomas , Fosfolípidos/metabolismo , Protectores contra Radiación/farmacología , Ácidos Esteáricos/farmacología , Administración Oral , Animales , Etanolaminas/administración & dosificación , Corazón/efectos de los fármacos , Corazón/efectos de la radiación , Microsomas/efectos de los fármacos , Microsomas/metabolismo , Microsomas/efectos de la radiación , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Microsomas Hepáticos/efectos de la radiación , Especificidad de Órganos , Protectores contra Radiación/administración & dosificación , Ratas , Ratas Wistar , Ácidos Esteáricos/administración & dosificación , Irradiación Corporal Total , Rayos XRESUMEN
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.
Asunto(s)
Etanolaminas/farmacología , Ácidos Grasos/metabolismo , Fosfolípidos/metabolismo , Daño por Reperfusión/metabolismo , Ácidos Esteáricos/farmacología , Animales , Masculino , Fosfolípidos/química , Ratas , Ratas WistarRESUMEN
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.
Asunto(s)
Colesterol/química , Etanolaminas/farmacología , Ácidos Grasos Insaturados/química , Ácidos Grasos/química , Miocardio/metabolismo , Daño por Reperfusión/metabolismo , Ácidos Esteáricos/farmacología , Animales , Técnicas In Vitro , Masculino , Ratas , Ratas WistarRESUMEN
Presented paper deals with the relationship between immunoglobulin polyreactive properties and its lipid composition. Serum blood immunoglobulin fraction of an intact rabbit as an experimental model was used. Immunoglobulins (Ig) obtained by this way were transformed into polyreactive immunoglobulins (PRIg) by treatment with chaotropic agent KSCN or reactive oxygen species (ROS) with usage of Fe2+, EDTA and ascorbic acid. It was demonstrated that native Ig were able to bind with immobilized antigen (ovalbumin) and this ability dramatically increased after transformation of Ig into PRIg. The high immunoreactivity of PRIg was associated with marked fall (by 2-3 fold) of total phospholipids as well as individual ones--sphingomyelin and phosphatidylcholine. The main fatty acids of the Ig and PRIg phospholipid fractions in the sequence to decreasing decrease were stearic, palmitic, oleic and linoleic acids. The treatment of Ig by chaotropic agent and ROS led to decrease of stearic acid and enhancement of oleic, linoleic and arachidonic acids. The level of free cholesterol of Ig did not differ from that of PRIg. At the same time the content of cholesterol esters of PRIg was substantially diminished if compare with Ig. The main fatty acids of the Ig and PRIg cholesterol ester fraction in the sequence to decreasing were arachidonic, stearic, oleic, linoleic and palmitoleic acids. Transformation of Ig into PRIg was accompanied by enhancement of stearic acid level and loss of docosapentaenoic, arachidonic and palmitoleic acids. The results presented here support the idea about non peroxidative manner of the phospholipid and cholesterol ester extrusion from Ig molecule under its transformation into PRIg. Rather the last process could be explained by the term of concurrent physico-chemical interaction of Ig molecule with chaotropic agent or ROS leading to fall of lipid content. The presented data for the first time provide us an opportunity to conclude that transformation of Ig into PRIG is associated with the marked loss of essential phospholipids and cholesterol esters by the Ig molecule. The probable implication of this process in development of immune imbalance under certain diseases associated with oxidative stress have been discussed.
Asunto(s)
Inmunoglobulinas/química , Lípidos/análisis , Animales , Ácido Ascórbico/química , Bovinos , Colesterol/análisis , Ácido Edético/química , Ácidos Grasos/análisis , Compuestos Ferrosos/química , Inmunoglobulinas/inmunología , Fosfolípidos/análisis , Conejos , Especies Reactivas de Oxígeno , Tiocianatos/químicaRESUMEN
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.
Asunto(s)
Paro Cardíaco Inducido/métodos , Cardiopatías Congénitas/cirugía , Metabolismo de los Lípidos , Miocardio/metabolismo , Niño , Cardiopatías Congénitas/metabolismo , Humanos , Lípidos/clasificaciónRESUMEN
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.
Asunto(s)
Membrana Eritrocítica/metabolismo , Ácidos Grasos/metabolismo , Isquemia Miocárdica/metabolismo , Estudios de Casos y Controles , Ácidos Grasos/clasificación , Humanos , Hipertensión/complicaciones , Isquemia Miocárdica/complicacionesRESUMEN
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.
Asunto(s)
Etanolaminas/metabolismo , Lípidos/fisiología , Contracción Miocárdica , Daño por Reperfusión Miocárdica/metabolismo , Animales , Etanolaminas/química , Técnicas In Vitro , Masculino , Sondas Moleculares , Fosfolipasa D/química , Ratas , Ratas WistarRESUMEN
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.
Asunto(s)
Glándulas Suprarrenales/efectos de los fármacos , Etanolaminas/farmacología , Receptor Cannabinoide CB2 , Glándulas Suprarrenales/metabolismo , Animales , Bovinos , Colesterol/metabolismo , Etanolaminas/química , Femenino , Cinética , Ratas , Receptores de Cannabinoides , Receptores de Droga/agonistasRESUMEN
The phospholipid composition of the myocardial tissue of the isolated rat heart under acute ischemia and effect of NSE on the level of phospholipid were studied. It was shown that the level of phospholipids and PI under ischemia increased by 15% and 25% respectively, but the level of DPG decreased by 14%. The addition of NSE into the perfusion medium prevents the alterations of phospholipids and DPG levels. This suggests that NSE has some cardioprotective properties.
Asunto(s)
Cardiotónicos/farmacología , Etanolaminas/farmacología , Isquemia Miocárdica/metabolismo , Miocardio/metabolismo , Fosfolípidos/metabolismo , Daño por Reperfusión/metabolismo , Ácidos Esteáricos/farmacología , Animales , Técnicas In Vitro , Masculino , Ratas , Ratas WistarRESUMEN
Data concerning the synthesis of bioactive lipid compound N-([1-14C]-palmitoyl)ethanolamine labeled by 14C fatty acid are reported. The method is based on the ability of ethanolamine and fatty acid to the direct chemical condensation at 180 degrees C with yielding of N-acylethanolamine. The purification of the end product by the double crystallization in ethanol allows to obtain chromatographically pure substance. The presented method of the labeled N-([1-14C]-palmitoyl)ethanolamine synthesis is simple and in extensive that's why it might be used in the area of biologically active compounds investigation.