The effect of N-stearoylethanolamine on the lipid composition of the rat testes and testosterone level during the early stages of streptozotocin-іnduced diabetes

Diabetes is a metabolic disorder with multiorgan complications, including reproductive system dysfunction where lipid imbalance of germ cells play an important role. N-stearoylethanolamine (NSE) shows a modulatory effect on the lipid composition under different pathologies. Therefore, the aim of our study was to investigate the NSE effect on the testes lipid composition and testosterone level in plasma of diabetic rats. Diabetes was induced in Sprague-Dawley rats by a single streptozotocin injection (50 mg/kg). Animals with glucose levels of 8-12 mmol/l were further selected. NSE was administrated to rats (50 mg/kg) for 10 days at 1.5 months after the streptozotocin injection. The rat testes were used for lipid analysis, namely, phospholipid level, fatty acid methyl esters and plasma testosterone estimation. NSE administration to diabetic rats triggered normalization of total and individual phospholipid content, as well as composition of free and phospholipids fatty acids in the rat testes. In addition, the testosterone content showed a slight increase under the action of NSE. Our results showed that the early stages of diabetes caused destructive changes in rat testes that may induce a decrease in future testicular function. NSE administration to diabetic rats normalized the lipid content of rat testes and was correlated with an increased testosterone level. NSE induced the restoration of testes structure and function during the early stages of streptozotocin-іnduced diabetes in rats

Preventive effect of N-stearoylethanolamine on memory disorders, blood and brain biochemical parameters in rats with experimental scopolamine-induced cognitive impairment

The impairment of cognitive functions is the most studied medical and social problem nowadays. The aim of this study was to evaluate the protective effects of N-stearoylethanolamine (NSE) on memory state, blood and brain biochemical parameters in rats under scopolamine-induced cognitive impairment. The results of this study shown that NSE administration to rats per os (5 mg/kg, 5 days, during last 3 days NSE was administrated 20 min prior to scopolamine injection (1 mg/kg, once daily for 3 days, intraperitoneally)) prevented the development of memory impairment. In particular, NSE action was associated with the prevention of increase in acetylcholinesterase activity, changes in phospholipid, free and esterified cholesterol level in hippocampus and frontal cortex, and disruption in pro-/antioxidant balance in blood and studied brain sections. Considering the above mentioned biological effects, NSE is a promising drug candidate for integrative therapy of cognitive impairment of different profiles

Modulation of LPS-induced ROS production and NF-κB nuclear translocation by N-stearoylethanolamine in macrophages

N-Stearoylethanolamine (NSE) is a minor lipid that belongs to the N-acylethanolamines family that mediates a wide range of biological processes. The effect of the NSE on reactive oxygen species (ROS) production and NF-κB activation stimulated by lipopolysaccharide (LPS) in rat peritoneal macrophages (PM) was evaluated. PM were obtained from the rat peritoneal cavity. ROS were detected following DCFDA and DHE fluorescence. Nuclear translocation of p65 NF-κB was examined by immunofluorescent method using confocal microscopy. It was shown that NSE exposure to peritoneal macrophages (10-7 M) prior to 30 min LPS stimulation inhibited super oxide and hydrogen peroxide production and NF-κB translocation into nuclei. Thus, NSE exhibits therapeutic potential to treat inflammatory diseases associated with increased activation of macrophages

The effect of N-stearoylethanolamine on adipocytes free cholesterol content and phospholipid composition in rats with obesity-induced insulin resistance

Obesity induces molecular changes that promote associated disorders, such as insulin resistance (IR) and type 2 diabetes. Low insulin sensitivity occurs primarily due to defects in the pathway of insulin action in target tissues, and there is a hypothesis that IR may originate in adipose tissue and is followed by dyslipidemia. In this study using methods of thin-layer and gas-liquid chromatography we investigated free cholesterol content and phospholipid composition of adipocytes of obesity-induced IR rats and its changes induced by the N-stearoylethanolamine (NSE) administration. The results we obtained demonstrated that free cholesterol content significantly increased in adipocytes of IR rats compared to control. The analysis of phospholipid composition indicated a reduction of phosphatidylcholine and the total content of phosphatidylinositol with phosphatidylserine, whereas the content of lysophosphatidylcholine, sphingomyelin and phosphatidylethanolamine increased in IR group compared to control. NSE administration caused a statistically significant decrease in total cholesterol level and had a considerable effect on normalization of individual phospholipids content. As far as NSE administration caused a statistically significant decrease in free cholesterol level and had a considerable effect on normalization of individual phospholipids content of adipocytes, we can consider NSE as a prospective compound worthy more complex investigation of its action under the pathological conditions

Blood coagulation and aortic wall integrity in rats with obesity-induced insulin resistance

Obesity is an important factor in pathogenesis of disorders caused by chronic inflammation. Diet-induced obesity leads to dyslipidemia and insulin resistance (IR) that in turn provoke the development of type 2 diabetes and cardiovascular diseases. Thus, the aim of this work was to investigate the possible pro-atherogenic effects in the blood coagulation system and aortic wall of rats with obesity-induced IR. The experimental model was induced by a 6-month high-fat diet (HFD) in white rats. Blood samples were collected from 7 control and 14 obese IR rats. Prothrombin time (PT) and partial activated thromboplastin time (APTT) were performed by standard methods using Coagulometer Solar СТ 2410. Fibrinogen concentration in the blood plasma was determined by the modified spectrophotometric method. Levels of protein C (PC), prothrombin and factor X were measured using specific chromogenic substrates and activa­ting enzymes from snake venoms. Platelet aggregation was measured and their count determined using Aggregometer Solar AP2110. The aorta samples were stained by hematoxylin and eosin according to Ehrlich. Aortic wall thickness was measured using morphometric program Image J. Statistical analysis was performed using Mann-Whitney U Test. The haemostasis system was characterized by estimation of the levels of individual coagulation factors, anticoagulant system involvement and platelet reactivity. PT and APTT demonstrated that blood coagulation time strongly tended to decrease in obese IR rats in comparison to the control group. It was also detec­ted that 30% of studied obese IR rats had decreased factor X level, 40% had decreased level of prothrombin whereas fibrinogen concentration was slightly increased up to 3 mg/ml in 37% of obese IR rats. A prominent decrease of anticoagulant PC in blood plasma of obese rats was detected. Obese IR rats also had increased platelet count and higher rate of platelet aggregation in comparison to control animals. Histological analysis identified the disruption of aorta endothelium and tendency for the thickening of the aorta wall in the group with obesity-induced IR compared to the group of control rats. Changes of individual coagulation factors were assumed as the evidence of imbalance in the blood coagulation system. Increase of fibrinogen level, drop in PC concentration and pathological platelet reactivity were taken to corroborate the development of low-grade inflammation in obese IR rats. Instant generation of small amounts of thrombin in their blood plasma is expected. Since the aorta morphology assay detected the trend of its wall to thicken and the emergence of disruptions, we assumed there were initial stages of atherosclerosis and the danger of developing atherothrombosis. We detected an increase of blood coagulability and changes in aorta morphology in rats with obesity-induced IR which we assume indicate early development of atherosclerosis

Antistress effects of N-stearoylethanolamine in rats with chronic social stress

The aim of this study was to evaluate the effects of N-stearoylethanolamine (NSE) on the number of biochemical parameters that are involved in the development of the stress response (corticosterone, catecholamines, testosterone, TBARS, nitric oxide, serotonin), memory state, exploratory activity and antinociceptive response in rats, using a model of chronic social stress. It has been demonstrated that administration of NSE (14 days , intragastrically, 50 mg/kg) after chronic social stress developed (stress was induced by daily agonistic interaction between animals), normalizes plasma content of corticosterone, testosterone, epinephrine, norepinephrine, dopamine, TBARS, nitrite-anion and increases serotonin level that leads to memory state improvement and increase in exploratory activity in rats. The tail-flick latency did not change, that is it remained at the level of stressed animals