N-Stearoylethanolamine Exerts Cardioprotective Effects in Old Rats


Cite item

Full Text

Abstract

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 results of different studies over the past decades have established the protective effect of NAE on many pathological conditions.

Objective:This study aimed to investigate the cardioprotective effects of C18:0 NAE— N-stearoylethanolamine (NSE) in aged rats. In this study, we focused on investigating the effects of C18:0 NAE— N-stearoylethanolamine (NSE) on the intensity of oxidative/ nitrosative stress, antioxidant potential, lipoprotein profile and inflammation markers of blood plasma, phospholipid composition and age-related morphological changes of old rat heart tissues.

Methods:The study was conducted on Sprague Dawley male laboratory rats. The three groups of rats were involved in the study design. The first group consisted of young rats aged 4 months (n=10). The second (n=10) and third (n=10) groups included old rats aged of 18 months. Rats from the third group were administered a per os aqueous suspension of NSE at a dose of 50 mg/kg of body weight daily for 10 days. All groups of rats were kept on a standard vivarium diet. The blood plasma, serum, and heart of rats were used for biochemical and histological analysis.

Results:The cardioprotective effect of N-stearoylethanolamine in old rats was established, which was expressed in the normalization of the antioxidant system condition and the level of proinflammatory cytokines, positive modulation of blood plasma and lipoprotein profile, normalization of heart tissue lipid composition, and significant reduction in age-related myocardium morphological changes.

Conclusion:The revealed effects of N-stearoylethanolamine can become the basis for developing a new drug for use in complex therapy to improve the quality of life of older people.

About the authors

Halyna Kosiakova

, OV Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine

Author for correspondence.
Email: info@benthamscience.net

Andrii Berdyshev

, OV Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine

Email: info@benthamscience.net

Tetyana Horid’ko

, OV Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine

Email: info@benthamscience.net

Olena Meged

, OV Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine

Email: info@benthamscience.net

Vitaliy Klimashevsky

, OV Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine

Email: info@benthamscience.net

Roza Matsokha

, OV Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine

Email: info@benthamscience.net

Oksana Tkachenko

, OV Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine

Email: info@benthamscience.net

Valentina Asmolkova

, OV Palladin Institute of Biochemistry of the National Academy of Sciences of Ukrain

Email: info@benthamscience.net

Tetyana Kvitnitskaya-Ryzhova

, DF Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine

Email: info@benthamscience.net

Serhii Luhovskyi

, DF Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine

Email: info@benthamscience.net

Pavlo Klymenko

, DF Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine

Email: info@benthamscience.net

Nadiya Hula

, OV Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine

Email: info@benthamscience.net

References

  1. Lloyd-Jones D, Adams R, Carnethon M, et al. American heart association statistics C and stroke statistics S.lstics--2009 update: A report from the american heart association statistics committee and stroke statistics subcommittee. Circulation 2009; 119(3): e182.
  2. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics--2015 update: A report from the american heart association. Circulation 2015; 131(4): e29-e322. doi: 10.1161/CIR.0000000000000152 PMID: 25520374
  3. Bencivenga L, Strumia M, Rolland Y, et al. Biomarkers of mitochondrial dysfunction and inflammaging in older adults and blood pressure variability. Geroscience 2023; 45(2): 797-809. doi: 10.1007/s11357-022-00697-y PMID: 36454336
  4. Lin ZC, Hsu CY, Hwang E, Wang PW, Fang JY. The role of cytokines/chemokines in an aging skin immune microenvironment. Mech Ageing Dev 2023; 210(210): 111761. doi: 10.1016/j.mad.2022.111761 PMID: 36496171
  5. Kiecolt-Glaser JK, Preacher KJ, MacCallum RC, Atkinson C, Malarkey WB, Glaser R. Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc Natl Acad Sci USA 2003; 100(15): 9090-5. doi: 10.1073/pnas.1531903100 PMID: 12840146
  6. Clinical, functional, and inflammatory characteristics of asthma among adults aged over 60 years old: A case-control study. J Asthma 2023; 7: 1-14.
  7. Tudorancea IM, Ciorpac M, Stanciu GD, et al. The therapeutic potential of the endocannabinoid system in age-related diseases. Biomedicines 2022; 10(10): 2492. doi: 10.3390/biomedicines10102492 PMID: 36289755
  8. Marzo VD, Bifulco M, Petrocellis LD. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov 2004; 3(9): 771-84. doi: 10.1038/nrd1495 PMID: 15340387
  9. Arner EC, Hughes CE, Decicco CP, Caterson B, Tortorella MD. Cytokine-induced cartilage proteoglycan degradation is mediated by aggrecanase. Osteoarthritis Cartilage 1998; 6(3): 214-28. doi: 10.1053/joca.1998.0114 PMID: 9682788
  10. Mock ED, Gagestein B, van der Stelt M. Anandamide and other Nacylethanolamines: A class of signaling lipids with therapeutic opportunities. Prog Lipid Res 2023; 89: 101194. doi: 10.1016/j.plipres.2022.101194 PMID: 36150527
  11. Schmid HHO, Berdyshev EV. Cannabinoid receptor-inactive N -acylethanolamines and other fatty acid amides: Metabolism and function. Prostaglandins Leukot Essent Fatty Acids 2002; 66(2-3): 363-76. doi: 10.1054/plef.2001.0348 PMID: 12052050
  12. Lambert DM, Di Marzo V. The palmitoylethanolamide and oleamide enigmas: Are these two fatty acid amides cannabimimetic? Curr Med Chem 1999; 6(8): 757-73. doi: 10.2174/0929867306666220401153732 PMID: 10469890
  13. Di Marzo V, Bisogno T, De Petrocellis L. The biosynthesis, fate and pharmacological properties of endocannabinoids. Handb Exp Pharmacol 2005; 168(168): 147-85. doi: 10.1007/3-540-26573-2_5 PMID: 16596774
  14. Hudz IA, Chernyshenko VO, Kasatkina LO, et al. N-Stearoylethanolamine inhibits integrin-mediated activation, aggregation, and adhesion of human platelets. J Pharmacol Exp Ther 2022; 383(1): 2-10. doi: 10.1124/jpet.122.001084 PMID: 35963618
  15. Lykhmus O, Kalashnyk O, Uspenska K, et al. Different effects of nicotine and n-stearoyl-ethanolamine on episodic memory and brain mitochondria of α7 nicotinic acetylcholine receptor knockout mice. Biomolecules 2020; 10(2): 226. doi: 10.3390/biom10020226
  16. Onopchenko OV, Kosiakova GV, Klimashevsky VM, Hula NM. The effect of N-stearoylethanolamine on plasma lipid composition in rats with experimental insulin resistance. Ukr Biochem J 2015; 87(1): 46-54. doi: 10.15407/ubj87.01.046 PMID: 26036130
  17. Onopchenko OV, Kosiakova GV, Goridko TM, Klimashevsky VM, Hula NM. The effect of N-stearoylethanolamine on liver phospholipid composition. Ukr Biochem J 2014; 86(1): 101-10. doi: 10.15407/ubj86.01.101 PMID: 24834723
  18. Onopchenko OV, Kosiakova HV, Horid’ko TM, Berdyshev AH, Mehed’ OF, Hula NM. 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. Ukr Biokhim Zh 2013; 85(5): 88-96.
  19. Gorid'ko TM, Kosiakova HV, Berdyshev AH, Bazylians'ka VR, Margitych VM, Gula NM. The influence of Nstearoylethanolamine 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. Ukr Biokhim Zh (1999) 2012; 84(3): 37-43.
  20. Voitychuk OI, Asmolkova VS, Gula NM, et al. Modulation of excitability, membrane currents and survival of cardiac myocytes by N-acylethanolamines. Biochim Biophys Acta Mol Cell Biol Lipids 2012; 1821(9): 1167-76. doi: 10.1016/j.bbalip.2012.05.003 PMID: 22613942
  21. Hula Hudz' IeA, Hula NM, Khmel TO, Horid'ko TM. Berdyshev AH. Antioxidative effect of the N-stearoylethanolamine in the heart tissue and blood plasma of rats under doxorubicin treatment Ukr Biokhim Zh (1999) 2011; 83(6): 86-91.
  22. Hula NM, Horid'ko TM, Stohniĭ NA. et al. Protective effect of Nstearoylethanolamine in acute alcohol intoxication in rats. Ukr Biokhim Zh (1999) 2010; 82(2): 42-52.
  23. Gulaia NM, Berdyshev AG, Chumak AA, Meged’ EF, Kindruk NL, Gorid’ko TN. Cardioprotective effect of Nstearoylethanolamine under the anaphylactic shock in guinea pigs. Biomed Khim 2009; 55(6): 743-9. PMID: 20469722
  24. Voĭtychuk OI, Asmolkova VS, Hula NM, Sotkis HV, Oz M. Shuba IaM. Regulation of the excitability of neonatal cardiomyocytes by N-stearoyl- and N-oleoyl-ethanolamines. Fiziol Zh (1994) 2009; 55(3): 55-66.
  25. Hula NM, Chumak AA, Mehed' OF, Horid'ko TM, Kindruk NL, Berdyshev AH. Immunosuppressive characteristics of N-stearoyl ethanolamine a stable compound with cannabimimetic activity Ukr Biokhim Zh (1999) 2008; 80(1): 57-67.
  26. Brosnan RJ, Eger EI II, Laster MJ, Sonner JM. Anesthetic properties of carbon dioxide in the rat. Anesth Analg 2007; 105(1): 103-6. doi: 10.1213/01.ane.0000265556.69089.78 PMID: 17578964
  27. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol 1959; 37(8): 911-7. doi: 10.1139/o59-099 PMID: 13671378
  28. Vaskovsky VE, Terekhova TA. HPTLC of phospholipid mixtures containing phosphatidylglycerol. J High Resolut Chromatogr 1979; 2(11): 671-2. doi: 10.1002/jhrc.1240021107
  29. Svetashev VI, Vaskovsky VE. A simplified technique for thin-layer microchromatography of lipids. J Chromatogr A 1972; 67(2): 376-8. doi: 10.1016/S0021-9673(01)91245-2 PMID: 5030903
  30. Techniques of lipidology: Isolation, analysis and identification of lipids, by M. Amsterdam, London: Kates, North-Holland Publishing Co. 1972.
  31. Vaskovsky VE, Kostetsky EY, Vasendin IM. A universal reagent for phospholipid analysis. J Chromatogr A 1975; 114(1): 129-41. doi: 10.1016/S0021-9673(00)85249-8 PMID: 1237496
  32. Tkachenko H, Kurhaluk N, Grudniewska J. Oxidative stress biomarkers in different tissues of rainbow trout (Oncorhynchus mykiss) exposed to Disinfectant-CIP formulated with peracetic acid and hydrogen peroxide. Arch Pol Fisheries 2014; 22(3): 207-19. doi: 10.2478/aopf-2014-0021
  33. Abdel-Tawab HM, Tarek MH, Samia MMM, Amel AR. Antioxidant potential and hepatoprotective activity of origanum majorana leaves extract against oxidative damage and hepatotoxicity induced by pirimiphos-methyl in male mice. J Appl Sci 2015; 15: 69-79.
  34. Gostukhina OL, Soldatov AA, Golovina IV, Borodina AV. Content of carotenoids and the state of tissue antioxidant enzymatic complex in bivalve mollusc Anadara inaequivalvis Br. Zh Evol Biokhim Fiziol 2012; 48(6): 542-7. PMID: 23401963
  35. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and 15Nnitrate in biological fluids. Anal Biochem 1982; 126(1): 131-8. doi: 10.1016/0003-2697(82)90118-X PMID: 7181105
  36. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72(1-2): 248-54. doi: 10.1016/0003-2697(76)90527-3 PMID: 942051
  37. Basic and Advanced Laboratory Techniques in Histopathology and Cytology/Pranab Dey. Springer Singapore 2018.
  38. Harman D. Aging: A theory based on free radical and radiation chemistry. J Gerontol 1956; 11(3): 298-300. doi: 10.1093/geronj/11.3.298 PMID: 13332224
  39. Baranov VS, Baranova EV. Aging and ambiguous ROS. System genetics analysis. Curr Aging Sci 2017; 10(1): 6-11. doi: 10.2174/1874609809666160921114504 PMID: 27659263
  40. Warner HR. Superoxide dismutase, aging, and degenerative disease. Free Radic Biol Med 1994; 17(3): 249-58. doi: 10.1016/0891-5849(94)90080-9 PMID: 7982630
  41. Nandi A, Yan LJ, Jana CK, Das N. Role of catalase in oxidative stress- and age-associated degenerative diseases. Oxid Med Cell Longev 2019; 2019: 1-19. doi: 10.1155/2019/9613090 PMID: 31827713
  42. Schriner SE, Linford NJ, Martin GM, et al. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 2005; 308(5730): 1909-11. doi: 10.1126/science.1106653 PMID: 15879174
  43. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: Biochemical role as a component of glutathione peroxidase. Science 1973; 179(4073): 588-90. doi: 10.1126/science.179.4073.588 PMID: 4686466
  44. Petropoulos I, Friguet B. Maintenance of proteins and aging: The role of oxidized protein repair. Free Radic Res 2006; 40(12): 1269-76. doi: 10.1080/10715760600917144 PMID: 17090416
  45. Rose AH, Hoffmann P. Selenoproteins and cardiovascular stress. Thromb Haemost 2015; 113(3): 494-504. doi: 10.1160/TH14-07-0603 PMID: 25354851
  46. Rikans LE, Hornbrook KR. Lipid peroxidation, antioxidant protection and aging. Biochim Biophys Acta Mol Basis Dis 1997; 1362(2-3): 116-27. doi: 10.1016/S0925-4439(97)00067-7 PMID: 9540842
  47. Salekeen R, Haider AN, Akhter F, Billah MM, Islam ME, Didarul Islam KM. Lipid oxidation in pathophysiology of atherosclerosis: Current understanding and therapeutic strategies. Int J Cardiol Cardiovasc Risk Preven 2022; 14: 200143. doi: 10.1016/j.ijcrp.2022.200143 PMID: 36060286
  48. Rizvi F, Preston CC, Emelyanova L, et al. Effects of aging on cardiac oxidative stress and transcriptional changes in pathways of reactive oxygen species generation and clearance. J Am Heart Assoc 2021; 10(16): e019948. doi: 10.1161/JAHA.120.019948 PMID: 34369184
  49. Ropelle ER, Pauli JR, Cintra DE, et al. Targeted disruption of inducible nitric oxide synthase protects against aging, S-nitrosation, and insulin resistance in muscle of male mice. Diabetes 2013; 62(2): 466-70. doi: 10.2337/db12-0339 PMID: 22991447
  50. Hula NM, Kosiakova HV, Kindruk NL, Khmel' TO. Effect of Nstearoylethanolamine on the level of stable NO metabolites in different pathological conditions which are accompanied by oxidative stress. Ukr Biokhim Zh (1999) 2005; 77(3): 113-9.
  51. Kosiakova HV, Hula NM. The N-stearoylethanolamine effect on the NO-synthase way of nitrogen oxide formation and phospholipid composition of erythrocyte membranes in rats with streptozotocine diabetes Ukr Biokhim Zh (1999) 2007; 76(9): 53-9.
  52. Sze SCW, Zhang L, Zhang S, et al. Aberrant Transferrin and Ferritin Upregulation Elicits Iron Accumulation and Oxidative Inflammaging Causing Ferroptosis and Undermines Estradiol Biosynthesis in Aging Rat Ovaries by Upregulating NF-Κb-Activated Inducible Nitric Oxide Synthase: First Demonstration of an Intricate Mechanism. Int J Mol Sci 2022; 23(20): 12689. doi: 10.3390/ijms232012689 PMID: 36293552
  53. McCANN SM. Mastronardi C, De Laurentiis A, Rettori V. The nitric oxide theory of aging revisited. Ann N Y Acad Sci 2005; 1057(1): 64-84. doi: 10.1196/annals.1356.064 PMID: 16399888
  54. Berdyshev AG, Kosiakova HV, Onopchenko OV, Panchuk RR, Stoika RS, Hula NM. N-Stearoylethanolamine suppresses the proinflammatory cytokines production by inhibition of NF-κB translocation. Prostaglandins Other Lipid Mediat 2015; 121(PtA): 91-6.
  55. Kosiakova H, Berdyshev A, Dosenko V, Drevytska T, Herasymenko O, Hula N. The involvement of peroxisome proliferatoractivated receptor gamma (PPARγ) in anti-inflammatory activity of N-stearoylethanolamine. Heliyon 2022; 8(11): e11336. doi: 10.1016/j.heliyon.2022.e11336 PMID: 36387464
  56. Hagen M, Derudder E. Inflammation and the alteration of b-cell physiology in aging. Gerontology 2020; 66(2): 105-13. doi: 10.1159/000501963 PMID: 31553969
  57. Gonçalves de Carvalho CMR, Ribeiro SML. Aging, low-grade systemic inflammation and vitamin D: A mini-review. Eur J Clin Nutr 2017; 71(4): 434-40. doi: 10.1038/ejcn.2016.177 PMID: 27677370
  58. Paradisi A, Oddi S, Maccarrone BSP. The endocannabinoid system in ageing: A new target for drug development. Curr Drug Targets 2006; 7(11): 1539-52. doi: 10.2174/1389450110607011539 PMID: 17100593
  59. Berrendero F, Romero J, García-Gil L, et al. Changes in cannabinoid receptor binding and mRNA levels in several brain regions of aged rats. Biochim Biophys Acta Mol Basis Dis 1998; 1407(3): 205-14. doi: 10.1016/S0925-4439(98)00042-8 PMID: 9748581
  60. Jiménez R, Sánchez M, Zarzuelo MJ, et al. Endothelium-dependent vasodilator effects of peroxisome proliferator-activated receptor beta agonists via the phosphatidyl-inositol-3 kinase-Akt pathway. J Pharmacol Exp Ther 2010; 332(2): 554-61. doi: 10.1124/jpet.109.159806 PMID: 19906781
  61. Crosby MB, Svenson J, Gilkeson GS, Nowling TK. A novel PPAR response element in the murine iNOS promoter. Mol Immunol 2005; 42(11): 1303-10. doi: 10.1016/j.molimm.2004.12.009 PMID: 15950726
  62. Liu HH, Li JJ. Aging and dyslipidemia: A review of potential mechanisms. Ageing Res Rev 2015; 19: 43-52. doi: 10.1016/j.arr.2014.12.001 PMID: 25500366
  63. Murawski U, Kriesten K, Egge H. Age-related changes of lipid fractions and total fatty acids in liver lipids and heart lipids of female and male rats aged 37–1200 days (liver) and 331–1200 days (heart). Comp Biochem Physiol B 1990; 96(2): 271-89. doi: 10.1016/0305-0491(90)90375-4 PMID: 2361362
  64. Nunes VS, da Silva Ferreira G, Quintão ECR. Cholesterol metabolism in aging simultaneously altered in liver and nervous system. Aging (Albany NY) 2022; 14(3): 1549-61. doi: 10.18632/aging.203880 PMID: 35130181
  65. Anandan R, Ganesan B, Obulesu T, et al. Antiaging effect of dietary chitosan supplementation on glutathione-dependent antioxidant system in young and aged rats. Cell Stress Chaperones 2013; 18(1): 121-5. doi: 10.1007/s12192-012-0354-2 PMID: 22828860
  66. Le Goff W, Guerin M, Chapman MJ. Pharmacological modulation of cholesteryl ester transfer protein, a new therapeutic target in atherogenic dyslipidemia. Pharmacol Ther 2004; 101(1): 17-38. doi: 10.1016/j.pharmthera.2003.10.001 PMID: 14729390
  67. Onopchenko OV, Kosiakova GV, Klimashevsky VM, Hula NM. The effect of N-stearoylethanolamine on plasma lipid composition in rats with experimental insulin resistance. Ukr Biochem J 2015; 87(1): 46-54. doi: 10.1038/83348 PMID: 11135616
  68. Hula NM, Horid'ko TM, Stohniĭ NA. Klimashevs'kyĭ VM, Mehed' OF, Kosiakova HV, Shovkun SA, Kindruk NL, Berdyshev AH. Protective effect of N-stearoylethanolamine in acute alcohol intoxication in rats. Ukr Biokhim Zh (1999) 2010; 82(2): 42-52. Ukrainian. PMID: 20684244
  69. Chinetti G, Lestavel S, Bocher V. Remaley AT, Neve B, Torra IP, Teissier E, Minnich A, Jaye M, Duverger N, Brewer HB, Fruchart JC, Clavey V, Staels B. PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med 2001; 7(1): 53-8. doi: 10.1038/83348 PMID: 11135616
  70. Iemitsu M, Miyauchi T, Maeda S. Tanabe T, Takanashi M, IrukayamaTomobe Y, Sakai S, Ohmori H, Matsuda M, Yamaguchi I. Aging-induced decrease in the PPAR-alpha level in hearts is improved by exercise training. Am J Physiol Heart Circ Physiol 2002; 283(5): H1750-60. doi: 10.1152/ajpheart.01051.2001 PMID: 12384451
  71. Ye P, Wang ZJ, Zhang XJ, Zhao YL. Age-related decrease in expression of peroxisome proliferator-activated receptor alpha and its effects on development of dyslipidemia. Chin Med J (Engl) 2005; 118(13): 1093-8. PMID: 16098262
  72. Kudryavtseva AV, Krasnov GS, Dmitriev AA. Alekseev BY, Kardymon OL, Sadritdinova AF, Fedorova MS, Pokrovsky AV, Melnikova NV, Kaprin AD, Moskalev AA, Snezhkina AV. Mitochondrial dysfunction and oxidative stress in aging and cancer. Oncotarget 2016; 7(29): 44879-905. doi: 10.18632/oncotarget.9821 PMID: 27270647
  73. Lazzeroni D, Villatore A, Souryal G, Pili G, Peretto G. The Aging Heart: A Molecular and Clinical Challenge. Int J Mol Sci 2022; 23(24): 16033. doi: 10.3390/ijms232416033 PMID: 36555671

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2024 Bentham Science Publishers