In the report of the World Health Organization from 1990 to 2016 to this day, Ukraine continues to occupy first place in the European region in morbidity and mortality from diseases of the cardiovascular system. One of the predictors and key links in the development of CVD is endothelial dysfunction. In this work, it was shown that chronic loading with sodium nitrite provokes the development of oxidative stress (an increase in 2,3-bisphosphoglyceric acid), inflammation (an increase in the level of interleukin-1-beta, which, in turn, causes a sharp increase in iNOS activity), the development of endothelial dysfunction (increase in von Willebrand factor). L-arginine alone, and in conjunction with the drug “Vin-Vita” cause a decrease in the negative effect of sodium nitrite

Gerasymenko, T. V.

Kryukovа, G. V.

Moiseieva, G.

Myastkivska, I. V.

Savitsky, I. V.

Yermuraki, P.

English

Akademicka Platforma Czasopism

 188 Savitsky I. V., Kryukovа G. V., Myastkivska I. V., Gerasymenko T. V., Moiseieva G., Yermuraki P. Еndothelial dysfunction due to sodium nitrite. Journal of Education, Health and Sport. 2020;10(3):188-198. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2020.10.03.021  https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2020.10.03.021  https://zenodo.org/record/5498080     The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2020; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper.  Received: 09.03.2020. Revised: 18.03.2020. Accepted: 31.03.2020.   ЕNDOTHELIAL DYSFUNCTION DUE TO SODIUM NITRITE  I. V. Savitsky2, G. V. Kryukovа1, I. V. Myastkivska1, T. V. Gerasymenko1,  G. Moiseieva2, P. Yermuraki1   1Odesa National Medical University, Odesa, Ukraine 2International European University, Kyiv, Ukraine   Abstract In the report of the World Health Organization from 1990 to 2016 to this day, Ukraine continues to occupy first place in the European region in morbidity and mortality from diseases of the cardiovascular system. One of the predictors and key links in the development of CVD is endothelial dysfunction. In this work, it was shown that chronic loading with sodium nitrite provokes the development of oxidative stress (an increase in 2,3-bisphosphoglyceric acid), inflammation (an increase in the level of interleukin-1-beta, which, in turn, causes a sharp increase in iNOS activity), the development of endothelial dysfunction (increase in von Willebrand factor). L-arginine alone, and in conjunction with the drug “Vin-Vita” cause a decrease in the negative effect of sodium nitrite. Key words: endothelial dysfunction; sodium nitrite; Vin-vit; bioflavonoids; L-arginine       189 РОЗВИТОК ЕНДОТЕЛІАЛЬНОЇ ДИСФУНКЦІЇ ПІД ВПЛИВОМ РОЗЧИНУ  НІТРИТУ НАТРІЮ  І. В. Савицький2, Г. В. Крюкова1, І. В. М'ястківська1, Т. В. Герасименко1,  Г. Мойсеєва2, П. Єрмуракі1   1Одеський національний медичний університет 2Міжнародний європейський університет Резюме У звіті Всесвітньої організації охорони здоров'я з 1990 по 2016 рік і донині Україна продовжує посідати перше місце в європейському регіоні за захворюваності і смертності від хвороб серцево-судинної системи. Одним із предикторів та провідною ланкою у розвитку патології серцево-судинної системи є ендотеліальна дисфункція. У даній роботі показано, що хронічне навантаження нітритом натрію провокує розвиток окисного стресу (збільшення 2,3-бісфосфогліцеріновой кислоти), запалення (підвищення рівня інтерлейкіну-1-бета, яке, в свою чергу, викликає різке збільшення активності iNOS), розвиток ендотеліальної дисфункції (збільшення фактора Віллебранда). Л-аргінін окремо, і в сукупності з препаратом "Вин-Віта" обумовлюють зниження негативного ефекту нітриту натрію. Ключові слова: ендотеліальна дисфункція; нітрит натрію; Він-Віта; біофлавоноїди; Л-аргінін                190 РАЗВИТИЕ ЭНДОТЕЛИАЛЬНОЙ ДИСФУНКЦИИ ПОД ВОЗДЕЙСТВИЕМ РАСТВОРА НИТРИТА НАТРИЯ  И. В. Савицкий2, Г. В. Крюкова1, И. В. Мястковская1, Т. В. Герасименко1,  А. Моисеева2, П. Ермураки1   1Одесский национальный медицинский университет 2Международный европейский университет Резюме В отчете Всемирной организации здравоохранения с 1990 по 2016 год и по сей день Украина продолжает занимать первое место в европейском регионе по заболеваемости и смертности от болезней сердечно-сосудистой системы. Одним из предикторов и ключевых звеньев в развитии патологии ССС является эндотелиальная дисфункция. В данной работе показано, что хроническая нагрузка нитритом натрия провоцирует развитие окислительного стресса (увеличение 2,3-бисфосфоглицериновой кислоты), воспаление (повышение уровня интерлейкина-1-бета, которое, в свою очередь, вызывает резкое увеличение активности iNOS), развитие эндотелиальной дисфункции (увеличение фактора Виллебранда). Л-аргинин отдельно, и в совокупности с препаратом “Вин-вита” обуславливают снижение негативного эффекта нитрита натрия.  Кючевые слова: эндотелиальная дисфункция; нитрит натрия; Вин-вита; биофлавоноиды; Л-аргинин   Relevance In the report of the World Health Organization from 1990 to 2016 and to this day, Ukraine continues to occupy first place in the European region in morbidity and mortality from diseases of the cardiovascular system. These disappointing statistics dictate to us the need for a thorough study of the factors affecting CVS. [1]. Including the vascular endothelium. Endothelial cells are a highly selective barrier and metabolic organ, and play an important role in the regulation of local homeostasis, immune function, maintaining a delicate balance between vasoconstrictor and vasodilator function. Chronic exposure to risk factors for cardiovascular disease and oxidative stress suppresses the protective mechanisms of vascular endothelium, followed by endothelial dysfunction.  191 According to many authors, endothelial dysfunction is one of the main pathogenetic links in the development of vascular disorders in the process of chronic diseases. Currently, the role of endothelial dysfunction in the development of diseases such as diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease, inflammatory bowel disease, etc. has been proven. In addition, ED is observed at an early stage of most cardiovascular diseases such as atherosclerosis, arterial hypertension, chronic heart failure. Therefore, early clinical detection of ED can be a critical point in the prevention of cardiovascular disease, because early detection of ED can be the initial reversible step in the development of these diseases. [2] Therefore, it is so necessary to study risk factors for the development of endothelial dysfunction and methods for their correction. The aim of the work was to study the development of endothelial dysfunction under the influence of sodium nitrite solution, as well as correction methods using l-arginine and antioxidant terrapia.  Materials and methods In our researches we used 40 auto breeding periadolescent Wistar male rets, body weight approximately 120 -150 grams , of which were formed four groups (ten heads each) by principle of analogy: • The first group - intact - on standard vivarium food and drink. • The second group received a 6,28 mg/kg (1/50 lethal dose) 0.2-1% solution of sodium nitrite intragastric.  • The third group receiving the above nitrite loading on the background of L-arginine (200 mg/kg), to study the effect of its compensatory properties in these conditions. • The fourth group receiving complex sodium nitrite, L-AR and Vin-Vitus (it contains bioflavonoids that will show us the effectiveness of antioxidant therapy). The duration of the diet is 1 month.  At the beginning of the experiment, as well as at the end of the second and fourth weeks, the weight of laboratory rats was measured to determine the effect of sodium nitrite and the nitric oxide cycle on the development of the body weight of rats in puberty.  All data obtained were processed by conventional biomedical research methods using statistical analysis by standard software packages. Mathematical processing included  192 calculations of arithmetic mean values (M), their errors (± m). The establishment of the probability of intergroup differences in the values of the change during the experiment was performed using the Student's parametric t-test. Differences were considered statistically significant at p ≤ 0.05.   Measurements blood changes Von Willebrand factor The von Willebrand factor is synthesized and secreted by the vascular endothelium to become part of the perivascular matrix. vWf promotes platelet adhesion in hemostasis by binding to a receptor on the platelet surface membrane (glycoprotein Ib / IX), thereby attaching platelets to the vessel wall. vWf is also required to maintain normal levels of plasma factor VIII. vWf levels can temporarily increase with stress, exercise, pregnancy, inflammation, or infections. [3] As we can see in annex 1, in the second group, which received a load of sodium nitrite solution, was a sharp increase in the relative concentration of sodium nitrite, above the permissible values. (p <0.001). This indicates a violation of the local regulation of hemostasis, and about  damage to the endothelium and the active development of the inflammatory reaction in the vessel wall.  In third the group, indicators are within the normal range, however, there is a statistically significant difference with the control group (p<0.05). That shows the compensatory properties of l-arginine on a chronic load of sodium nitrite. In the fourth group using the Vin-Vita, the indicators did not make a statistically significant difference with the control group, and amounted to 89.3% (±10.2%). Rats intake of l -arginine with antioxidant therapy reduces the negative effects of sodium nitrite.            193  [annex 1]   2,3-Bisphosphoglyceric acid  2,3-BPG interacts with deoxygenated hemoglobin beta subunits and so it decreases the affinity for oxygen and allosterically promotes the release of the remaining oxygen molecules bound to the hemoglobin; [4] therefore, it enhances the ability of RBCs to release oxygen near tissues that need it most.  A statistically significant increase in 2,3-BPG in all groups indicates tissue hypoxia.            194 [annex 2]    Interleukin 1-beta   Interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine that is crucial for host-defence responses to infection and injury [1] . It is produced and secreted  within cells of the innate immune system, such as monocytes and macrophages. It is produced in response to molecular motifs carried by pathogens called 'pathogen associated molecular patterns' (PAMPs).  An increase in interleukin in the second and third group indicates an inflammatory reaction. (p <0.01).            195  [annex 6]    L-arginine level  Arginine is a necessary precursor for the synthesis of proteins and many biologically important molecules, such as ornithine, proline, polyamines, creatine and agmatine. However, the main role of arginine in the human body is to be a substrate for the synthesis of nitric oxide (NO). [6] A statistically significant (p <0.01) decrease in the amount of arginine in the blood of rats indicates the presence of negative feedback with exogenous intake of sodium nitrite. In the second and third groups, no statistical difference is observed, which is associated with the simultaneous exogenous intake of l-arginine as well.           196  [annex 7]    Expression of inducible and endothelial nitric oxide synthase  In the second group, the activity of eNOS has statistically significant difference (p <0.01). This indicates the progression of endothelial dysfunction.  A statistically significant increase (p <0.01) of iNOS activity indicates the presence of inflammation in the vessel wall.  In groups with a compensatory effect, the situation with activity of enzymes improves, however, there is still a statistically significant difference.             197  [annex 8]    Conclusions 1) А constant load of sodium nitrite occurs:   oxidative stress (an increase in 2,3-bisphosphoglyceric acid),   inflammation (an increase in interleukin-1 beta, which in turn causes a sharp increase in iNOS activity),  the development of endothelial dysfunction (an increase in von Willebrand factor).   2) A decrease in the level of l-arginine in the group that received sodium nitrite indicates a negative feedback between the level of sodium nitrite and l-arginine.  3) A sharp decrease in eNOS activity indicates the progression of endothelial dysfunction.-  4) The use of l-AR led to a relative or complete compensation for the action of  198 sodium nitrite. 5) The use of a bioflavonoid almost completely compensated for the effect of sodium nitrite.  Reference 1) Toni Meier, Kira Gräfe, Franziska Senn, Cardiovascular mortality attributable to dietary risk factors in 51 countries in the WHO European Region from 1990 to 2016: a systematic analysis of the Global Burden of Disease Study. European Journal of Epidemiology volume 34, pages 37–55 (2019) 2) Kyoung-Ha Park and Wu Jung Park, Clinical Implications in Cardiovascular Disease and Therapeutic Approaches Journat Korean Med Sci.; 30(9): 1213–1225. (2015 Sep) 3) Joel L. Moake Overview of Hemostasis. Nov 2018 Avalible: https://www.msdmanuals.com/professional/hematology-and-oncology/hemostasis/overview-of-hemostasis  Mulquiney, PJ, Bubb, WA; Kuchel, PW Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations: in vivo kinetic characterization of 2,3-bisphosphoglycerate synthase/phosphatase using 13C and 31P NMR . Biochem J . 342 (3): 567–80 (1999).  4) Gloria LC, David B,  Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev.  Aug; 22(4): 189–195. (2011) 5) Heinzen EL , Pollack GM, Pharmacokinetics and pharmacodynamics of l-arginine in rats: a model of stimulated neuronal nitric oxide synthesis Avalible: https://doi.org/10.1016/S0006-8993(03)03370-5 

Еndothelial dysfunction due to sodium nitrite

Savitsky I. V., Kryukovа G. V., Myastkivska I. V., Gerasymenko T. V., Moiseieva G., Yermuraki P. Еndothelial dysfunction due to sodium nitrite. Journal of Education, Health and Sport. 2020;10(3):188-198. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2020.10.03.021

https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2020.10.03.021

https://zenodo.org/record/5498080

 

 

 

 

The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019.

© The Authors 2020;

This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland

Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium,

provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike.

(http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited.

The authors declare that there is no conflict of interests regarding the publication of this paper.

 

Received: 09.03.2020. Revised: 18.03.2020. Accepted: 31.03.2020.

 

 

ЕNDOTHELIAL DYSFUNCTION DUE TO SODIUM NITRITE

I. V. Savitsky2, G. V. Kryukovа1, I. V. Myastkivska1, T. V. Gerasymenko1,

G. Moiseieva2, P. Yermuraki1


1Odesa National Medical University, Odesa, Ukraine

2International European University, Kyiv, Ukraine

 

Abstract

In the report of the World Health Organization from 1990 to 2016 to this day, Ukraine continues to occupy first place in the European region in morbidity and mortality from diseases of the cardiovascular system. One of the predictors and key links in the development of CVD is endothelial dysfunction. In this work, it was shown that chronic loading with sodium nitrite provokes the development of oxidative stress (an increase in 2,3-bisphosphoglyceric acid), inflammation (an increase in the level of interleukin-1-beta, which, in turn, causes a sharp increase in iNOS activity), the development of endothelial dysfunction (increase in von Willebrand factor). L-arginine alone, and in conjunction with the drug “Vin-Vita” cause a decrease in the negative effect of sodium nitrite.

Key words: endothelial dysfunction; sodium nitrite; Vin-vit; bioflavonoids; L-arginin

NEUROSURGERY ENTHUSIASTIC WOMEN SOCIETY

https://apcz.umk.pl/JEHS/article/download/JEHS.2020.10.03.021/29650

Еndothelial dysfunction due to sodium nitrite

Abstract

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