Tag Archives: N-stearoylethanolamine

Diet-induced and age-related changes in rats: the impact of N-stearoylethanolamine intake on plasma lipoproteins, adiponectin, and adipocyte cholesterol-phospholipid composition

O. S. Tkachenko*, H. V. Kosiakova

Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv, Ukraine;
*e-mail: 888oksana.tkachenko@gmail.com

Received: 26 January 2024; Revised: 19 March 2024;
Accepted: 19 March 2024; Available on-line: 30 April 2024

Adiponectin is secreted by adipose tissue, associated with lipoprotein (LP) metabolism, down-regulated­ in insulin resistance states, and reduced in individuals suffering from obesity and cardiovascular diseases. Phospholipids and cholesterol are the main components of cell membranes and play a critical role in storage and secretory adipocyte functions. N-stearoylethanolamine (NSE) is a minor lipid affecting cell membrane lipids’ composition. Our study aimed to investigate plasma levels of adiponectin and cholesterol of low- and high-density LP (LDL and HDL) and adipocyte cholesterol-phospholipid (Chol-PL) composition of different age rats with high-fat diet (HFD)-induced obesity and insulin resistance and their changes under NSE administration. Our study demonstrated that chronic dietary fat overloading leads to obesity accompanied by impairment of glucose tolerance, a manifestation of dyslipidemia, and changes in plasma adiponectin levels in rats from two age groups (10-month-old and and 24-month-old). Prolonged HFD led to a reduction in plasma adiponectin levels and the growth of adipocyte cholesterol content in rats of different ages. A significant increase in plasma LDL-Chol level and main adipocyte PLs (phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and lysophosphatidylcholine) was observed in younger rats, whereas not detected in elder animals after dietary fats overloading. The decrease in the content of anionic phospholipids (phosphatidylinositol + phosphatidylserine) was also detected in 10-month-old HFD rats compared to the control animals. NSE administration positively affected the normalization of adiponectin levels in both age HFD groups. It significantly impacted the reduction of LDL-Chol levels and the growth of HDL-Chol concentration in the blood plasma of 10-month-old rats as well as PL-composition of young HFD rats and anionic PL restoring in 24-month-old rats. The positive effect on investigated parameters makes NSE a prospective agent for treating diet-induced and age-related metabolic disorders threatening cardiovascular diseases.

Multifunctional chitosan-based hydrogels: characterization and evaluation of biocompatibility and biodegradability in vitro

N. Manko1, M. Lootsik1, V. Antonyuk1,2, I. Ivasechko1,
N. Skorokhyd1, H. Kosiakova3, O. Mehed’3, T. Horid’ko3,
N. Hula3, O. Klyuchivska1, R. Panchuk1, N. Pokhodylo4,
О. Barabash4, T. Dumych2, R. Stoika1,4*

1Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
2Danylo Halytsky National Medical University of Lviv, Lviv, Ukraine;
3Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
4Ivan Franko National University of Lviv, Lviv, Ukraine;
*e-mail: stoika.rostyslav@gmail.com

Received: 29 November 2023; Revised: 31 December 2023;
Accepted: 01 February 2024; Available on-line: 26 February 2024

Creation of novel remedies efficient in supporting wound healing remains an actual task in pharmacology. Hydrogels showed high efficiency in wound healing and tissue regeneration due to viscosity, elasticity and fluidity that provide them with functional characteristics similar to that in extracellular matrix. The aim of the study was to create chitosan-based hydrogels functionalized with different components (chondroitin-6-sulfate, hyaluronic acid, N-stearoylethanolamine) and to estimate their biocompatibility and biodegradabili­ty in vitro. For the first time, a lipid substance N-stearoylethanolamine (NSE) known as suppressor of pro-inflammatory cytokines expression was used as hydrogel component (1.95 mg/g). FTIR analysis confirmed the complexation of chitosan molecule with hyaluronate, chondroitin-6-sulfate, NSE. MTT-test and Trypan blue exclusion test were used to study hydrogels cytotoxicity towards human cells of different tissue origin. Biodegradability of hydrogels was evaluated using direct hydrogel contact with cells and cell-independent degradation. It was shown that chondroitin-6-sulfate (<2 mg/ml), hyaluronic acid (<2 mg/ml) and NSE (26 µg/ml) did not demonstrate significant toxic effects towards pseudonormal human cells of the MCF10A, HaCat, HEK293 lines and mouse cells of the Balb/3T3 line. The studied hydrogels were stable in saline solution, while in a complete culture medium containing 10% fetal bovine blood serum they underwent degradation in >24 h. The identified biodegradability of the chitosan-based hydrogels is important for the release of noncovalently immobilized NSE into biological medium. Further studies on laboratory animals with experimental wounds are expected to explore the potential of created hydrogels as anti-inflammatory and wound-healing agents.

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

O. V. Onopchenko*, T. M. Horid’ko, H. V. Kosiakova,
A. G. Berdyshev, V. M. Klimashevsky, N. M. Hula

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: onop.89.av@gmail.com

Received: 23 December 2019; Accepted: 27 March 2020

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

T. M. Horid’ko1, H. V. Kosiakova1, A. G. Berdyshev1, O. F. Meged1,
O. V. Onopchenko1, V. M. Klimashevsky1, О. S. Tkachenko1, V. R. Bazylianska1,
V. O. Kholin2, K. O. Peschana2, S. A. Mykhalskiy2, N. M. Hula1

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2Institute of Gerontology, National Academy of Medical Sciences of Ukraine, Kyiv;
e-mail: TanGoRi@ukr.net

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.

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

O. S. Dziuba, Ie. A. Hudz, H. V. Kosiakova, T. M. Horid’ko, V. M. Klimashevsky, N. M. Hula

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: oksana.dziuba86@gmail.com

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.

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

I. A. Goudz, N. M. Gula, T. O. Khmel, T. M. Goridko, A. G. Berdyshev

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: ngula@biochem.kiev.ua

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.

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

A. G. Berdyshev, H. V. Kosiakova, N. M. Hula

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: kievlipids@gmail.com

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.

Antitoxical effects of N-stearoylethanolamine in suspension and in nanocomposite complex in the organs of mice with the Lewis carcinoma under doxorubicin administration

I. A. Goudz1, N. M. Gula1, T. O. Khmel1, T. M. Goridko1, Y. M. Bashta1,
R. R. Panchuk2, R. S. Stoika2, A. A. Ryabtseva3, O. S. Zaichenko3

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: ngula@biochem.kiev.ua;
2Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
3National University Lviv Politekhnika, Ukraine

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.

Effect of N-stearoylethanolamine on the DNA fragmentation intensity in tumour and extratumoral tissues of the human adrenal cortex

N. I. Levchuk1, V. M. Pushkarev1, O. I. Kovzun1,
A. S. Mikosha1, N. M. Gula2, M. D. Tronko1

1State Institution V. P. Komisarenko Institute of Endocrinology and Metabolism,
National Academy of Medical Sciences of Ukraine, Kyiv;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: levnataly@meta.ua

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.