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 plasma lipid composition in rats with experimental insulin resistance

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

The effect of N-stearoylethanolamine on cholesterol content, fatty acid composition and protein carbonylation level in rats with alimentary obesity-induced insulin resistance

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 and a 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 of protein 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

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

N-stearoylethanolamine effect on the level of 11-hydroxycorticosteroids, cytokines IL-1β, IL-6 and TNFα 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. There was also found a significant decrease of cytokines (IL-1β, IL-6 and TNFα) levels under the NSE action. This way may be one of the mechanisms of NSE anti-inflammatory action