Tag Archives: N-stearoylethanolamine

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.

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-іnduced diabetes

T. M. Goridko, G. V. Kosiakova, A. G. Berdyschev,
V. R. Bazylyanska, V. M. Margitich, N. M. Gula

Palladin Institute of Biochemistry, National Academy of Science of Ukraine, Kyiv;
e-mail: TanGori@ukr.net

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.
The per os administration of the NSE aqueous suspension in a dose of 50 mg/kg during 10 days to the rats with induced diabetes contributed to the normalization of catalase activity in the testis, which correlated with a decrease in the amount of TBA-reacting products and activity of superoxide dismutase and catalase in the blood plasma of animals; the use of NSE also contributed to the reduction of nitrite content in the gonads and to normalization of both nitrite and nitrate in the blood plasma of rats. The NSE administration to intact animals caused an increase in superoxide dismutase activity and significantly reduced the content of stable NO metabolites in the blood plasma of animals.

Antitoxic and antioxidant effects of N-stearoylethanolamin in the content of nanocomposite complex with doxorubicin in organs of mice with Lewis carcinoma

E. A. Gudz1, N. M. Hula1, T. N. Goridko1, Y. M. Bashta1,
A. I. Voyeikov1, A. G. Berdyshev1, H. V. Kosiakova2,
R. R. Panchuk3, 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 Biology of Cell, National Academy of Sciences of Ukraine, Lviv;
3National University “Lvov Politekhnika”, Ukraine

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.

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

O. V. Onopchenko, G. V. Kosiakova, T. M. Goridko,
A. G. Berdyschev, O. F. Meged, N. M. Hula

Palladin Institute of Biochemistry, National Academy of Science of Ukraine, Kyiv;
e-mail: onop.89.av@mail.ru

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 glucosotolerance 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.

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

O. V. Onopchenko, G. V. Kosiakova, E. F. Meged,
V. M. Klimashevsky, N. M. Hula

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

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.

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

A. D. Zhukov, A. G. Berdyshev, G. V. Kosiakova, V. M. Klimashevskiy,
T. M. Gorid’ko, O. F. Meged, N. M. Hula

Palladin Institute of Biochemistry, National Academy of Science of Ukraine, Kyiv;
e-mail: joblipids@hotmail.com

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.

The effect of N-stearoylethanolamine on liver phospholipid composition of rats with insulin resistance caused by alimentary obesity

O. V. Onopchenko, G. V. Kosiakova, T. M. Goridko, V. M. Klimashevsky, N. M. Hula

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

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.