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1.
Probl Radiac Med Radiobiol ; 25: 75-89, 2020 Dec.
Article in English, Ukrainian | MEDLINE | ID: mdl-33361830

ABSTRACT

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.


Subject(s)
Chernobyl Nuclear Accident , Endocannabinoids/therapeutic use , Fatigue Syndrome, Chronic/pathology , Mental Disorders/pathology , Radiation Exposure/adverse effects , Radiation Injuries/pathology , Dose-Response Relationship, Radiation , Endocannabinoids/metabolism , Fatigue Syndrome, Chronic/etiology , Fatigue Syndrome, Chronic/metabolism , Fatigue Syndrome, Chronic/therapy , Humans , Mental Disorders/etiology , Mental Disorders/metabolism , Mental Disorders/therapy , Nervous System/pathology , Nervous System/radiation effects , Neurons/pathology , Neurons/radiation effects , Radiation Dosage , Radiation Injuries/etiology , Radiation Injuries/metabolism , Radiation Injuries/therapy , Radiation, Ionizing , Receptors, Cannabinoid/metabolism , Time Factors
2.
Ukr Biochem J ; 87(1): 46-54, 2015.
Article in English | MEDLINE | ID: mdl-26036130

ABSTRACT

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.


Subject(s)
Dietary Fats/adverse effects , Ethanolamines/pharmacology , Insulin Resistance , Lipid Metabolism/drug effects , Obesity/blood , Obesity/drug therapy , Stearic Acids/pharmacology , Animals , Animals, Outbred Strains , Diet, High-Fat , Fatty Acids, Monounsaturated/blood , Fatty Acids, Nonesterified/blood , Fatty Acids, Unsaturated/blood , Lipoproteins, HDL/blood , Lipoproteins, LDL/blood , Lipoproteins, VLDL/blood , Obesity/etiology , Obesity/pathology , Rats , Triglycerides/blood , Tumor Necrosis Factor-alpha/blood
3.
Ukr Biochem J ; 86(3): 88-97, 2014.
Article in Ukrainian | MEDLINE | ID: mdl-25033558

ABSTRACT

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.


Subject(s)
11-Hydroxycorticosteroids/blood , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Burns/drug therapy , Ethanolamines/pharmacology , Skin/drug effects , Stearic Acids/pharmacology , Wound Healing/drug effects , Administration, Cutaneous , Animals , Burns/blood , Burns/immunology , Burns/pathology , Hot Temperature , Inflammation/blood , Inflammation/drug therapy , Inflammation/immunology , Inflammation/pathology , Interleukin-1beta/blood , Interleukin-6/blood , Male , Rats , Rats, Wistar , Skin/immunology , Skin/injuries , Tumor Necrosis Factor-alpha/blood , Wound Healing/physiology
4.
Ukr Biochem J ; 86(1): 101-10, 2014.
Article in Ukrainian | MEDLINE | ID: mdl-24834723

ABSTRACT

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.


Subject(s)
Ethanolamines/pharmacology , Fatty Acids, Unsaturated/chemistry , Liver/metabolism , Obesity/drug therapy , Obesity/metabolism , Phospholipids/chemistry , Stearic Acids/pharmacology , Animals , Blood Glucose/metabolism , Body Weight/drug effects , Diet, High-Fat/adverse effects , Disease Models, Animal , Fatty Acid Desaturases/metabolism , Fatty Acids, Unsaturated/metabolism , Insulin/blood , Insulin Resistance , Liver/drug effects , Liver/pathology , Male , Obesity/etiology , Obesity/pathology , Phospholipids/metabolism , Rats
5.
Fiziol Zh (1994) ; 60(5): 52-61, 2014.
Article in Ukrainian | MEDLINE | ID: mdl-25566671

ABSTRACT

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.


Subject(s)
Anti-Anxiety Agents/pharmacology , Anxiety/prevention & control , Cognition/drug effects , Emotions/drug effects , Ethanolamines/pharmacology , Maze Learning/drug effects , Motor Activity/drug effects , Stearic Acids/pharmacology , Animals , Behavior, Animal , Cognition/physiology , Conditioning, Psychological/drug effects , Dose-Response Relationship, Drug , Drug Administration Schedule , Emotions/physiology , Male , Maze Learning/physiology , Motor Activity/physiology , Rats
6.
Ukr Biochem J ; 86(6): 119-28, 2014.
Article in English | MEDLINE | ID: mdl-25816612

ABSTRACT

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.


Subject(s)
Cholesterol/metabolism , Ethanolamines/pharmacology , Fatty Acids, Monounsaturated/metabolism , Fatty Acids, Nonesterified/metabolism , Fatty Acids, Unsaturated/metabolism , Hypolipidemic Agents/pharmacology , Obesity/drug therapy , Stearic Acids/pharmacology , Animals , Diet, High-Fat , Dietary Fats/adverse effects , Insulin Resistance , Liver/drug effects , Liver/metabolism , Male , Obesity/etiology , Obesity/metabolism , Protein Carbonylation , Rats , Rats, Sprague-Dawley , Streptozocin/administration & dosage
7.
Ukr Biokhim Zh (1999) ; 85(2): 45-51, 2013.
Article in Ukrainian | MEDLINE | ID: mdl-23808309

ABSTRACT

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.


Subject(s)
Antioxidants/therapeutic use , Carcinoma, Lewis Lung/drug therapy , Doxorubicin/toxicity , Ethanolamines/therapeutic use , Kidney/drug effects , Liver/drug effects , Myocardium/enzymology , Stearic Acids/therapeutic use , Alanine Transaminase/blood , Alanine Transaminase/metabolism , Animals , Antioxidants/administration & dosage , Antioxidants/metabolism , Aspartate Aminotransferases/blood , Aspartate Aminotransferases/metabolism , Blood Urea Nitrogen , Carcinoma, Lewis Lung/blood , Carcinoma, Lewis Lung/enzymology , Creatinine/blood , Dose-Response Relationship, Drug , Doxorubicin/therapeutic use , Ethanolamines/administration & dosage , Kidney/enzymology , Kidney/metabolism , Liver/enzymology , Male , Mice , Myocardium/metabolism , Organ Specificity , Stearic Acids/administration & dosage
8.
Ukr Biokhim Zh (1999) ; 85(5): 88-96, 2013.
Article in Ukrainian | MEDLINE | ID: mdl-24479326

ABSTRACT

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.


Subject(s)
Ethanolamines/pharmacology , Hyperglycemia/drug therapy , Insulin Resistance , Liver/drug effects , Nitric Oxide/antagonists & inhibitors , Stearic Acids/pharmacology , Animals , Animals, Outbred Strains , Blood Glucose/metabolism , Catalase/metabolism , Diet, High-Fat , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Hyperglycemia/chemically induced , Hyperglycemia/metabolism , Insulin/blood , Lipid Peroxidation/drug effects , Liver/enzymology , Male , Nitric Oxide/metabolism , Rats , Streptozocin/pharmacology , Superoxide Dismutase/metabolism
9.
Ukr Biokhim Zh (1999) ; 85(5): 97-104, 2013.
Article in Ukrainian | MEDLINE | ID: mdl-24479327

ABSTRACT

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.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Antioxidants/pharmacology , Carcinoma, Lewis Lung/drug therapy , Doxorubicin/pharmacology , Ethanolamines/pharmacology , Stearic Acids/pharmacology , Alanine Transaminase/blood , Animals , Antibiotics, Antineoplastic/chemistry , Antioxidants/chemistry , Aspartate Aminotransferases/blood , Carcinoma, Lewis Lung/metabolism , Catalase/antagonists & inhibitors , Catalase/metabolism , Creatinine/blood , Doxorubicin/chemistry , Ethanolamines/chemistry , Glutathione Peroxidase/metabolism , Heart/drug effects , Kidney/drug effects , Kidney/metabolism , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Nanocomposites , Polyethylene Glycols/chemistry , Stearic Acids/chemistry , Superoxide Dismutase/antagonists & inhibitors , Superoxide Dismutase/metabolism
10.
Ukr Biokhim Zh (1999) ; 84(4): 49-53, 2012.
Article in Ukrainian | MEDLINE | ID: mdl-22946300

ABSTRACT

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.


Subject(s)
Adrenal Glands/drug effects , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , DNA Fragmentation/drug effects , Ethanolamines/pharmacology , Stearic Acids/pharmacology , Adrenal Cortex Hormones/metabolism , Adrenal Gland Neoplasms/drug therapy , Adrenal Gland Neoplasms/metabolism , Adrenal Gland Neoplasms/pathology , Adrenal Glands/metabolism , Adrenal Glands/pathology , Cushing Syndrome/drug therapy , Cushing Syndrome/metabolism , Cushing Syndrome/pathology , Drug Resistance, Neoplasm , Humans , Hyperplasia/drug therapy , Hyperplasia/metabolism , Hyperplasia/pathology , Microtomy , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Organ Specificity , Tissue Culture Techniques , Tumor Microenvironment
11.
Ukr Biokhim Zh (1999) ; 84(4): 61-9, 2012.
Article in Ukrainian | MEDLINE | ID: mdl-22946302

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/adverse effects , Antioxidants/therapeutic use , Carcinoma, Lewis Lung/drug therapy , Doxorubicin/adverse effects , Ethanolamines/therapeutic use , Lung Neoplasms/drug therapy , Stearic Acids/therapeutic use , Alanine Transaminase/metabolism , Animals , Antineoplastic Agents/administration & dosage , Antioxidants/administration & dosage , Aspartate Aminotransferases/metabolism , Biomarkers/metabolism , Carcinoma, Lewis Lung/enzymology , Doxorubicin/administration & dosage , Drug Carriers/administration & dosage , Ethanolamines/administration & dosage , Female , Heart/drug effects , Kidney/drug effects , Kidney/enzymology , Liver/drug effects , Liver/enzymology , Lung Neoplasms/enzymology , Mice , Nanocomposites/administration & dosage , Stearic Acids/administration & dosage , Urea/blood
12.
Ukr Biokhim Zh (1999) ; 84(2): 89-92, 2012.
Article in Ukrainian | MEDLINE | ID: mdl-22642126

ABSTRACT

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.


Subject(s)
Antihypertensive Agents/administration & dosage , Diabetes Mellitus, Experimental/drug therapy , Ethanolamines/administration & dosage , Hypertension, Renal/drug therapy , Peptidyl-Dipeptidase A/metabolism , Stearic Acids/administration & dosage , Administration, Oral , Animals , Antihypertensive Agents/therapeutic use , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/enzymology , Ethanolamines/therapeutic use , Hippocampus/drug effects , Hippocampus/metabolism , Hypertension, Renal/complications , Hypertension, Renal/enzymology , Hypothalamus/drug effects , Hypothalamus/metabolism , Male , Pituitary Gland, Anterior/drug effects , Pituitary Gland, Anterior/metabolism , Rats , Renin-Angiotensin System/drug effects , Stearic Acids/therapeutic use
13.
Ukr Biokhim Zh (1999) ; 83(6): 86-91, 2011.
Article in Ukrainian | MEDLINE | ID: mdl-22364023

ABSTRACT

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.


Subject(s)
Doxorubicin/pharmacology , Ethanolamines/pharmacology , Heart/drug effects , Myocardium/metabolism , Plasma/drug effects , Stearic Acids/pharmacology , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Creatinine/blood , Doxorubicin/blood , Drug Interactions , Ethanolamines/blood , Glutathione Peroxidase/metabolism , Myocardium/enzymology , Oxidation-Reduction , Plasma/chemistry , Rats , Stearic Acids/blood , Superoxide Dismutase/metabolism , Urea/blood
14.
Ukr Biokhim Zh (1999) ; 82(2): 42-52, 2010.
Article in Ukrainian | MEDLINE | ID: mdl-20684244

ABSTRACT

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.


Subject(s)
Alcoholic Intoxication/prevention & control , Ethanol/toxicity , Ethanolamines/therapeutic use , Protective Agents/therapeutic use , Stearic Acids/therapeutic use , Acute Disease , Alcoholic Intoxication/blood , Alcoholic Intoxication/metabolism , Animals , Antioxidants/metabolism , Brain/drug effects , Brain/enzymology , Brain/metabolism , Cell Membrane/drug effects , Cell Membrane/enzymology , Cell Membrane/metabolism , Disease Models, Animal , Ethanolamines/administration & dosage , Fatty Acids/metabolism , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/enzymology , Liver/metabolism , Nitric Oxide/blood , Nitric Oxide/metabolism , Protective Agents/administration & dosage , Rats , Stearic Acids/administration & dosage , Thiobarbituric Acid Reactive Substances/metabolism
15.
Fiziol Zh (1994) ; 56(5): 13-22, 2010.
Article in Ukrainian | MEDLINE | ID: mdl-21265075

ABSTRACT

The group of N-acylethanolamines (NAE) includes lipids that are capable of modulating plasma membrane ion channels without involvement of cannabinoid receptors. However, the action of various members of NAE on voltage-gated Na+ channels (VGSC) in cardiac tissue is still not fully elucidated. Here using patch-clamp technique we have studied the modulation of biophysical properties of VGSC of neonatal cardiomyocytes by saturated N-stearoylethanolamine (NSE) and monounsaturated N-oleoylethanolamine (OEA). NSE in 1-200 tM concentration range did not significantly alter the amplitude of inward Na+ current (I(Na)), but 100 microM NSE shifted its steady-state activation and inactivation curves in hyperpolarization direction by 2.4 mV and 10.6 mV, respectively. Activation kinetics of the current was not changed by NSE, but its inactivation was accelerated by about 1.2-fold in the -60 - -30 mV range of membrane potentials. Unlike NSE, OEA dose-dependently inhibited I(Na) with kappa(D) = 11.4 +/- 1.6 microM and maximal block at saturating concentration of 30 +/- 3%. It also stronger than NSE shifted current's steady-state activation and inactivation curves (-6.4 mV and -14.0 mV, respectively, at 100 microM) in hyperpolarization direction. The effect of OEA on I(Na) activation kinetics was negligible, but it more pronouncedly than NSE accelerated inactivation of the current. Thus, both members of NAE influence the voltage-dependence of activation, inactivation and kinetics of I(Na). These effects were more prominent for monounsaturated OEA, which also partially blocked I(Na). The discovered effects of NSE and OEA on VGSCs may in part be responsible for the decrease of cardiomycytes' excitability by these lipids under normal as well as pathologic conditions.


Subject(s)
Ethanolamines/pharmacology , Myocytes, Cardiac/drug effects , Sodium Channels/metabolism , Stearic Acids/pharmacology , Animals , Animals, Newborn , Cell Culture Techniques , Cell Membrane/drug effects , Cell Membrane/metabolism , Cells, Cultured , Endocannabinoids , Ion Transport/drug effects , Membrane Potentials/drug effects , Myocytes, Cardiac/metabolism , Oleic Acids , Patch-Clamp Techniques , Rats
16.
Ukr Biokhim Zh (1999) ; 82(4): 33-9, 2010.
Article in Ukrainian | MEDLINE | ID: mdl-21516714

ABSTRACT

Effects of N-stearoylethanolamine (NSE), N-oleoilethanolamine (OEA) and mixture of more than 20 saturated and unsaturated N-acylethanolamines on phospholipids composition of normal and transformed fibroblasts in the culture were compared in the work. It was shown that cultivation of cells NSE decreases percent content of phosphatidylinositol (PI), phosphatidylserine (PS) and sphingomyeline (SM) - important mediators of cell signaling. Under the influence of OEA the level of SM decreases as well, but at the same time PI and PS levels increase. NAEs mixture decreases PS and PI levels in cells and causes phosphatidylcholine (PC) amount increase. Moreover NSE and NAEs mixture decrease the content of main mitochondria membrane lipid - diphosphatidylglicerole (DPG). OEA increases DPG amount. In transformed fibroblasts (line L929) NAE modulate lipid composition as well: NSE decreases the level of phosphatidylethanolamine (PE), OEA and NAEs mixture increase sphingomyeline levels. It is shown that response of normal and transformed fibroblasts on NAE application is different, depending on substance structure and cell-target type.


Subject(s)
Cell Transformation, Neoplastic/drug effects , Ethanolamines/pharmacology , Fibroblasts/drug effects , Phospholipids/metabolism , Animals , Animals, Newborn , Cell Culture Techniques , Cell Line , Cell Membrane/metabolism , Cell Transformation, Neoplastic/metabolism , Ethanolamines/chemistry , Fatty Acids/metabolism , Fibroblasts/metabolism , Rats , Structure-Activity Relationship
17.
Ukr Biokhim Zh (1999) ; 82(3): 18-23, 2010.
Article in Ukrainian | MEDLINE | ID: mdl-21328874

ABSTRACT

The influence of N-stearoylethanolamine (NSE) on total 11-hydroxycorticosteroids (11-HCS) and testosterone level in the blood of male rats in normal conditions and under the action of 17beta-estradiol (400 mkg/kg of body weight during 3 days) was studied. It was shown that NSE administration per os (50 mg/kg of body weight during 7 days) to intact animals did not change the level of 11-HCS and of testosterone. The administration of NSE to estrogenized male rats decreased the elevated level of 11-HCS and normalized the amount of testosterone in blood. The correction of alterated weight of adenohypophysis and testis of estrogenized male rats compared to control can be a direct evidence of NSE-mediated modelling of the effect on hypothalamic-pituitary hormone system. The effect of NSE in the testis of estrogenized male rats inhibited the process of lipid peroxidation, caused the decrease of the amount of thiobarbituric acid reactive substances and increased the activity of superoxide dismutase and catalase. The NSE showed more expressed antioxidative effect compared to vitamin E. Taking into consideration all above mentioned data we suggested that NSE administration to male rats protected Leydig cells from damage under the increase of estrogen level.


Subject(s)
Antioxidants/pharmacology , Estradiol/adverse effects , Ethanolamines/pharmacology , Models, Biological , Stearic Acids/pharmacology , Testis/drug effects , 11-Hydroxycorticosteroids/blood , Animals , Leydig Cells/drug effects , Leydig Cells/metabolism , Lipid Peroxidation/drug effects , Male , Rats , Testis/metabolism , Testosterone/blood
18.
Ukr Biokhim Zh (1999) ; 81(3): 108-16, 2009.
Article in Ukrainian | MEDLINE | ID: mdl-19877436

ABSTRACT

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.


Subject(s)
Cell Proliferation/drug effects , Ethanolamines/pharmacology , Fibroblasts/drug effects , Glycerolphosphate Dehydrogenase/metabolism , Mitochondria/drug effects , Stearic Acids/pharmacology , Succinate Dehydrogenase/metabolism , Animals , Apoptosis/drug effects , Cell Line, Transformed , Cell Line, Tumor , Cell Survival/drug effects , Electron Transport , Fibroblasts/enzymology , Mice , Mitochondria/enzymology , Time Factors
19.
Ukr Biokhim Zh (1999) ; 81(2): 107-16, 2009.
Article in Ukrainian | MEDLINE | ID: mdl-19873884

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Burns/drug therapy , Ethanolamines/therapeutic use , Skin/drug effects , Stearic Acids/therapeutic use , Administration, Cutaneous , Administration, Oral , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Antioxidants/administration & dosage , Antioxidants/pharmacology , Burns/enzymology , Burns/immunology , Burns/metabolism , Catalase/blood , Catalase/metabolism , Disease Models, Animal , Erythrocytes/drug effects , Erythrocytes/enzymology , Erythrocytes/metabolism , Ethanolamines/administration & dosage , Ethanolamines/pharmacology , Glutathione Reductase/blood , Glutathione Reductase/metabolism , Interleukin-6/blood , Interleukin-6/immunology , Liver/drug effects , Liver/enzymology , Nitric Oxide Synthase/metabolism , Rats , Skin/enzymology , Skin/injuries , Skin/metabolism , Spleen/drug effects , Spleen/enzymology , Stearic Acids/administration & dosage , Stearic Acids/pharmacology , Superoxide Dismutase/blood , Superoxide Dismutase/metabolism , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/immunology , Wound Healing/drug effects
20.
Fiziol Zh (1994) ; 55(3): 55-66, 2009.
Article in Ukrainian | MEDLINE | ID: mdl-19526857

ABSTRACT

N-acylethanolamines (NAE) are biologically active lipids able of modulating ion transport through the cellular plasma membrane, however specific targets of their action and signalling mechanisms involved in cardiac tissue are still poorly understood. Physiological activity of NAEs is known to depend on the level of unsaturation. Therefore, here we investigated the effects of saturated N-stearylethanolamine (NSE) and monounsaturated N-oleylethanolamine on electric excitability of neonatal rat cardiomyocytes. 1 microM of either NSE or OEA decreased the duration of cardiac action potential (AP) from all parts of heart muscle. Shortening of AP was partially reversible, though the reversibility of AP duration upon washout of substances was more complete for endocardial ventricular compared to epicardial and atrial cardiomyocytes. I microM NSE depolarized resting membrane potential (RMP) of epicardial and of 65% of endocardial cells, whilst other cells types showed weakly reversible hyperpolarization. 1 microM OEA caused reversible RMP hyperpolarization of all studied cell types. NSE and OEA decreased the amplitude and upstroke velocity of AP that suggests their effect on sodium channels. NSE and to a lesser extent OEA inhibited the amplitude of AP phase 2 (plateau) which may indicate an inhibition of high-voltage-activated calcium channels. Effects of NSE and OEA on RMP and repolarization phase of AP (phase 3) depended on cardiac cell type suggesting differential regulation of inward rectifier Kir and voltage-gated delayed rectifier potassium channels by these lipids. We cannot also exclude interaction of NSE and OEA with anion channels, backgound K+ channels and ion transporters of the cardiomyocytes' plasma membrane. Overall, NSE-induced changes of AP parameters were less reversible than those induced by OEA, suggesting a slower degradation/ convertion of NSE in plasma membrane compared to OEA.


Subject(s)
Action Potentials/drug effects , Cell Membrane/drug effects , Ethanolamines/pharmacology , Myocytes, Cardiac/drug effects , Stearic Acids/pharmacology , Animals , Animals, Newborn , Cell Membrane/metabolism , Cells, Cultured , Endocannabinoids , Ion Transport/drug effects , Myocytes, Cardiac/metabolism , Oleic Acids , Potassium Channels/metabolism , Rats , Sodium Channels/metabolism
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