N-Stearoylethanolamine Exerts Cardioprotective Effects in Old Rats.

Background: Aging is associated with the slowing down of metabolic processes, diminished physiological processes, changes in hormonal activity and increasing exposure to oxidative stress factors and chronic inflammation. The endocannabinoid system (ECS) is a major signaling network that plays a pro-homeostatic role in the central and peripheral organs of the human body. A class of minor lipids, N-acylethanolamines (NAEs), which do not activate cannabinoid receptors, except for anandamide, but can potentiate the action of endocannabinoids and have a wide spectrum of biological activity and significant adaptogenic potential, belongs to ECS.

The involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in anti-inflammatory activity of N-stearoylethanolamine.

Background: N-stearoylethanolamine (NSE) is a bioactive lipid amine with a wide range of biological activities. Anti-inflammatory properties of NSE were previously confirmed on multiple animal models. However, the molecular mechanisms of anti-inflammatory action of NSE remain unclear.

RADIATION DAMAGE OF THE NERVOUS SYSTEM AND ENDOCANABINOIDS.

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.

Knowledge-based isocenter selection in radiosurgery planning.

Purpose: We present a new method for knowledge-based isocenter selection for treatment planning in radiosurgery. Our objective is to develop a prediction model that can learn from past manually designed treatment plans. We leverage recent advances in deep learning to predict isocenter locations in treatment plans in order to provide a decision support tool.

Simultaneous optimization of isocenter locations and sector duration in radiosurgery.

Stereotactic radiosurgery is an effective technique to treat brain tumors for which several inverse planning methods may be appropriate. We propose an integer programming model to simultaneous sector duration and isocenter optimization (SDIO) problem for Leksell Gamma Knife Icon (Elekta, Stockholm, Sweden) to tractably incorporate treatment time. We devise a Benders decomposition scheme to solve the SDIO problem to optimality.

Modeling and comparison of alternative approaches for sector duration optimization in a dedicated radiosurgery system.

Stereotactic radiosurgery (SRS) is an effective technique to treat brain metastasis for which several inverse planning methods may be appropriate. We compare three different optimization models for segment duration optimization in SRS using Leksell Gamma Knife Icon (Elekta, Stockholm, Sweden). We investigate (1) a linear programming approach, (2) a piecewise quadratic penalty approach, and (3) an unconstrained convex moment-based penalty approach.

Transgeneration effects of N-stearoylethanolamine in irradiated rats.

Objective: to explore possible transgeneration effects in the rats offspring of the first generation of parents subject ed to the combined effects of N stearoylethanolamine (NSE) and external exposure.Materials and metods. In the first generation rats of both sexes born to parents who have experienced the combined influence of ionizing radiation at a dose of 2.

Potential use of N-stearoylethanolamine in radiation medicine.

A new class of biologically active compounds N-acylethanolamines with properties of endogenous cannabinoids are considered in the terms of promising use in radiation medicine both in the acute phase for the prevention and treatment of ionizing radiation damage and in remote period for the treatment of the effects of exposure.

N-Stearoylethanolamine suppresses the pro-inflammatory cytokines production by inhibition of NF-κB translocation.

N-Stearoylethanolamine (NSE) is a minor lipid that belongs to the N-Acylethanolamines family that mediates a wide range of biological processes. This study investigates the mechanisms of anti-inflammatory action of NSE on different model systems. Namely, we estimated the effect of NSE on inflammatory cytokines mRNA level (leukemia cells L1210), cytokines content (serum and LPS-stimulated macrophages) and nuclear translocation of NF-κB (peritoneal macrophages LPS-stimulated and isolated from rats with obesity-induced insulin resistance).

Peculiarity of changes of peripheral blood hematological indices in rats under N-stearoilethanolamine administration conditioned by combined effects of ionizing radiation and stress.

Unlabelled: Objective - to investigate the peculiarities of peripheral blood indices changes in rats under the N-stearoiletanolamine treatment before and after combined effects of ionizing radiation and stress.

Methods: hematological, statistical.

Results: Per oral administration of NSE (10,0 mg / kg) before and after the combined effects of single whole-body irradiation (6.

[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.

[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.

[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 influence of N-stearoylethanolamine on the activity of antioxidant enzymes and on the level of stable NO metabolites in the rat testes and blood plasma at the early stages of streptozotocine-induced diabetes].

The influence of N-stearoylethanolamine was investigated on the activity of enzymes of antioxidant protection and content of stable metabolites of nitric oxide (NO) in the testes and plasma of rats at the early stages of development of streptozotocine-induced diabetes mellitus. It was shown that the activity of superoxide dismutase, catalase is reduced in the plasma and testes of animals with streptozotocin-induced (50 mg/kg) diabetes (blood glucose 8-10 mmol/L). A significant increase in the amount of nitrite and nitrate anions was revealed in the plasma of rats, while only the level of nitrite was significantly changed in the testes of animals.

[Antioxidative effect of the N-stearoylethanolamine in the heart tissue and blood plasma of rats under doxorubicin treatment].

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.

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

The effect of the endocannabinoid congener N-stearoylethanolamine (NSE) on the content of plasma and liver free amino acids in burned rats was studied. The animals after the thermal burn of the skin received per os during 7 days the water suspension of NSE in the doze 10 mg/kg of body weight. In the other group of rats the suspension was applied on the wound (the concentration of NSE was 10 mg/ml).

[The modelling of N-stearoylethanolamine effect of 17beta-estradiol in the organism of male rats].

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.

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

The influence of N-stearoylethanolamine on the nitric oxide system, the state of lipid peroxidation, antioxidant enzyme activity, content of phospholipids and fatty acids were studied under the acute ethanol intoxication (2.5 g/kg) in rats. The results of investigations show that acute ethanol intoxication caused abnormalities of the oxidative homeostasis accompanied by the accumulation of thiobarbituric acid reactive substances (TBARS).

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

It was shown for the first time that endogenous cannabimimetic compound N-stearoylethanolamine (NSE) administered at the dose 65 mg/kg of body weight during two weeks before anaphylaxis had cardioprotective properties on the model of anaphylactic shock in the guinea pigs. NSE reliably normalized the content of histamine and nitric oxide, decreased the activity both inducible and constitutive NO-synthases, prevented accumulation of thiobarbituric acid reactive substances (TBARS) and normalized the activity of catalase, superoxide dismutase and glutathione peroxidase in cardiomyocytes of animals under anaphylaxis. About of 70% of the NSE-treated animals survived under the anaphylactic shock.

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

The biochemical mechanisms of anti-inflammatory effect of endocannabinoid congener N-stearoylethanolamine (NSE) was studied on the model of experimental burn in rats. The animals after the thermal burn of the skin received per os during 7 days the water suspension of NSE in a doze 10 mg/kg of body weight. In the other groups of rats the suspension was applied to the wound (the concentration of NSE was 10 mg/ml).

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

Results of investigation of biochemical mechanisms of N-stearoylethanolamine (NSE) influence on the processes of allergic responses of immediate and delayed type (anaphylactic shock in guinea pigs and contact hypersensitivity to 2,4-dinitrochlorobenzene in mice) are presented in the paper. NSE was given per os during two weeks. It was found that in anaphylactic animals, NSE prevented the growth of histamine levels in the heart, kidneys and spleen, suppressed NO2(-) level increase in these organs and promoted its normalization.

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

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

[The effects of n-stearoylethanolamine on the NO-synthase pathway of NO generation in the aorta and heart of streptozotocin-induced diabetic rats].

The aim of the presented experiments was to study the influence of suturated NAE--N-stearoylethanolamine (NSE) on the NO synthesis by NO-synthases in aorta and heart tissues of rats with developmental (12-week) streptozotocin-induced (50 mg/kg of body weight) diabetes. Also we evaluated the state of endothelium-dependent relax reactions of aorta smooth muscles. It was shown that the development of diabetes is accompanied with disbalance of NO-synthesis wich consist in inducible NOS (iNOS) activation and inhibition of constitutive NOS (cNOS) and arginase activities.

[Changes of nitric oxide level at different stages of primary open-angle glaucoma].

The contents of NO stable metabolites in tears, and blood serum of the patients with different stages of open-angle glaucoma have been studied. The increasing of NO stable metabolite contents was found in tears, aqueous humor and blood serum during glaucoma progression. The depletion of glaucoma pathogenesis oxidative link was found at the terminal stage of the disease.