urmjУральский медицинский журналUral Medical Journal2949-4389Ural State Medical University10.52420/umj.23.2.98QPVVKDurmj-1500Research ArticleОригинальные статьи | Original articlesOriginal articlesКоррекция нитрозативного стресса при репаративной регенерации слизистой оболочки полости носа в экспериментеCorrection of Nitrosative Stress During Reparative Regeneration of the Nasal Cavity Mucosa in an Experimentalhttps://orcid.org/0000-0003-1694-341XБерестИ. Е.BerestI. Ye.

Ирина Евгеньевна Берест — кандидат медицинских наук, доцент кафедры оториноларингологии и офтальмологии

Луганск

Irina Ye. Berest — Candidate of Sciences (Medicine), Associate Professor of the Department of Otorhinolaryngology and Ophthalmology

Lugansk

i_berest@mail.ruЛуганский государственный медицинский университет имени Святителя ЛукиРоссияSt. Luke’s Lugansk State Medical UniversityRussian Federation20241005202423298105Copyright © Берест И.Е., 20242024Берест И.Е.Berest I.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.umjusmu.ru/jour/article/view/1500Введение

Введение. Метаболиты оксида азота играют важную роль в пролонгации воспалительной реакции, нарушениях регенерации эпителия при заболеваниях верхних дыхательных путей. Одним из перспективных подходов к регуляции биоактивности оксида азота является применение антиоксидантов.

Цель исследования — оценить эффективность применения антиоксидантной терапии для коррекции нитрозативного стресса при репаративной регенерации слизистой оболочки полости носа в эксперименте.

Материалы и методы

Материалы и методы. Проведено доклиническое рандомизированное экспериментальное исследование на 160 крысах-самцах, распределенных на 4 группы. Контрольную группу (n = 40) составили интактные животные. Животным экспериментальной группы 1 (n = 40) после травмы не проводилось лечение, в группе

2 (n = 40) назначалось противовоспалительное лечение. Группу 3 составили лабораторные крысы (n = 40), которым дополнительно в полость носа вводили препарат с антиоксидантными свойствами — 15 % раствор диметилового эфира 1,1-диметил-3-оксобутилфосфоновой кислоты. На 2, 5, 10 и 14 сутки наблюдения в крови животных определяли концентрацию нитратов и нитритов, C-реактивного белка.

Результаты

Результаты. В группе 3 после повышения на 2 день после травмы уровня метаболитов оксида азота на 5 сутки отмечалось значительное (р ≤ 0,05) его снижение в сравнении с другими группами, а к 10 суткам — нормализация показателя. Повышение уровня C-реактивного белка в сыворотке крови коррелировало с концентрацией метаболитов оксида азота.

Обсуждение

Обсуждение. Оптимальный терапевтический эффект при приеме антиоксидантов развивается при назначении в первые часы после травмы. Однако длительность приема не должна превышать 4–5 суток для избегания значительного снижения уровня метаболитов оксида азота и ухудшения регенерации слизистой оболочки.

Заключение

Заключение. Оценка показателей метаболитов оксида азота в крови в разные сроки после травмы является важным маркером активности воспаления. Применение антиоксидантов способствует снижению концентрации активных радикалов азота.

Introduction

Introduction. Nitric oxide metabolites play an important role in prolongation of the inflammatory reaction, disorders of epithelial regeneration in diseases of the upper respiratory tract. One of the promising approaches to regulating the bioactivity of nitric oxide is the use of antioxidants.

The objective of the study is to evaluate the effectiveness of antioxidant therapy for the correction of nitrosative stress during reparative regeneration of the nasal mucosa in an experiment.

Methods

Methods. A preclinical randomized experimental study is conducted on 160 rats, divided into 4 groups. The control group (n = 40) consists of intact animals. Animals in experimental group 1 (n = 40) do not receive treatment aſter injury; in group 2 (n = 40) anti-inflammatory treatment is prescribed. The third group consists of laboratory rats (n = 40), which are additionally injected into the nasal cavity with an antioxidant — a 15 % solution of 1,1-dimethyl-3-oxobutylphosphonic acid dimethyl ester. On days 2, 5, 10, and 14 of observation, the concentration of nitrates and nitrites and C-reactive protein in the blood of animals are determined.

Results

Results. In group 3, aſter an increase in the level of nitric oxide metabolites on day 2 aſter injury on day 5, a significant (p < 0.05) decrease was noted in comparison with other groups, and by day 10— normalization of the indicator. An increase in the level of C-reactive protein in blood serum correlated with the concentration of nitric oxide metabolites.

Discussion

Discussion. The optimal therapeutic effect when taking antioxidants develops when administered in the first hours aſter injury to reduce the excessive formation of reactive nitrogen radicals. However, the duration of administration should not exceed 4–5 days to avoid a significant decrease in the level of nitric oxide metabolites and deterioration of mucosal regeneration.

Conclusions

Conclusions. Assessment of nitric oxide metabolitesin the blood at different times aſter injury is an important marker of inflammatory activity. The use of antioxidants helps to reduce the concentration of active nitrogen radicals.

нитрозативный стрессоксид азотавоспалениеслизистая оболочкаантиоксидантnitrosative stressnitric oxideinflammationmucous membraneantioxidantReferencesDadali VA. Pathogenesis of nitrosative stress and approaches to modulating NO levels in organs and tissues. Therapist. 2023;4:52–58. (In Russ.). DOI: http://doi.org/10.33920/MED-12-2304-06.Dadali VA. Pathogenesis of nitrosative stress and approaches to modulating NO levels in organs and tissues. Therapist. 2023;4:52–58. (In Russ.). DOI: http://doi.org/10.33920/MED-12-2304-06.Ghimire K, Altmann HM, Straub AC, Isenberg JS. Nitric oxide: What’s new to NO? American Journal of Physiology-Cell Physiology. 2017;312(3):C254–C262. DOI: https://doi.org/10.1152/ajpcell.00315.2016.Ghimire K, Altmann HM, Straub AC, Isenberg JS. Nitric oxide: What’s new to NO? American Journal of Physiology-Cell Physiology. 2017;312(3):C254–C262. DOI: https://doi.org/10.1152/ajpcell.00315.2016.Soodaeva SK, KlimanovIA, Nikitina LYu. Nitrosative and oxidative stressesin respiratory diseases. Russian Pulmonology. 2017;27(2):262–273. (In Russ.). DOI: https://doi.org/10.18093/0869-0189-2017-27-2-262-273.Soodaeva SK, KlimanovIA, Nikitina LYu. Nitrosative and oxidative stressesin respiratory diseases. Russian Pulmonology. 2017;27(2):262–273. (In Russ.). DOI: https://doi.org/10.18093/0869-0189-2017-27-2-262-273.Jeong H, Choi D, Tanum J, Oh Y, Park K, Hong J. Nanocrystals continuously releasing nitric oxide: Promoting cell migration and increasing cell survival against oxidative stress. Chemistry of Materials. 2020;32(22):9787– 9797. DOI: https://doi.org/10.1021/acs.chemmater.0c03800.Jeong H, Choi D, Tanum J, Oh Y, Park K, Hong J. Nanocrystals continuously releasing nitric oxide: Promoting cell migration and increasing cell survival against oxidative stress. Chemistry of Materials. 2020;32(22):9787– 9797. DOI: https://doi.org/10.1021/acs.chemmater.0c03800.Pozhilova EV, Novikov VE. Physiological and pathological value of cellular synthase of nitrogen oxide and endogenous nitrogen oxide. Vestnik of Smolensk State Medical Academy. 2015;14(4):35–41. (In Russ.). EDN: https://elibrary.ru/vnvyfz.Pozhilova EV, Novikov VE. Physiological and pathological value of cellular synthase of nitrogen oxide and endogenous nitrogen oxide. Vestnik of Smolensk State Medical Academy. 2015;14(4):35–41. (In Russ.). EDN: https://elibrary.ru/vnvyfz.Titov VJu, Vertiprahov VG, Dolgorukova AM, Osipov AN. Synthesis and metabolism of nitric oxide in physiological processes and inflammation. Bioradikaly i antioksidanty. 2018;5(3):243–246. (In Russ.). EDN: https://elibrary.ru/vjqqbm.Titov VJu, Vertiprahov VG, Dolgorukova AM, Osipov AN. Synthesis and metabolism of nitric oxide in physiological processes and inflammation. Bioradikaly i antioksidanty. 2018;5(3):243–246. (In Russ.). EDN: https://elibrary.ru/vjqqbm.Abd El-Aleem SA, Mohammed HH, Saber EA, Embaby AS, Djouhri L. Mutual inter-regulation between iNOS and TGF-β1: Possible molecular and cellular mechanisms of iNOS in wound healing. Biochimica et Biophysica Acta (BBA) — Molecular Basis of Disease. 2020;1866(10):165850. DOI: https://doi.org/10.1016/j.bbadis.2020.165850.Abd El-Aleem SA, Mohammed HH, Saber EA, Embaby AS, Djouhri L. Mutual inter-regulation between iNOS and TGF-β1: Possible molecular and cellular mechanisms of iNOS in wound healing. Biochimica et Biophysica Acta (BBA) — Molecular Basis of Disease. 2020;1866(10):165850. DOI: https://doi.org/10.1016/j.bbadis.2020.165850.Arhipova LT, Arhipova MM, Levanova OG. Тhe role of nitric oxide in the pathogenesis of postoperative intraocular inflammation in the experimental surgical injury of both eyes. Russian Ophthalmological Journal. 2012;5(3):75–80. (In Russ.). EDN: https://elibrary.ru/qclned.Arhipova LT, Arhipova MM, Levanova OG. Тhe role of nitric oxide in the pathogenesis of postoperative intraocular inflammation in the experimental surgical injury of both eyes. Russian Ophthalmological Journal. 2012;5(3):75–80. (In Russ.). EDN: https://elibrary.ru/qclned.Edranov SS. Cellular and molecular aspects of posttraumatic regeneration of the mucosa of the paranasal sinuses. Pacific Medical Journal. 2016;(2):67–71. (In Russ.). EDN: https://elibrary.ru/vuyokz.Edranov SS. Cellular and molecular aspects of posttraumatic regeneration of the mucosa of the paranasal sinuses. Pacific Medical Journal. 2016;(2):67–71. (In Russ.). EDN: https://elibrary.ru/vuyokz.Wu M, Lu Z, Wu K, Nam C, Zhang L, Guo J. Recent advances in the development of nitric oxide-releasing biomaterials and their application potentials in chronic wound healing. Journal of Materials Chemistry B. 2021;9(35):7063–7075. DOI: https://doi.org/10.1039/d1tb00847a.Wu M, Lu Z, Wu K, Nam C, Zhang L, Guo J. Recent advances in the development of nitric oxide-releasing biomaterials and their application potentials in chronic wound healing. Journal of Materials Chemistry B. 2021;9(35):7063–7075. DOI: https://doi.org/10.1039/d1tb00847a.Kartopolova EV, Ratnikova LI. Etiological and pathogenetic features of modern influenza (Analytical review of the scientific literature). Izvestija vysshih uchebnyh zavedenij. Ural’skij region. 2016;(2):143–147. (In Russ.). EDN: https://elibrary.ru/wiryax.Kartopolova EV, Ratnikova LI. Etiological and pathogenetic features of modern influenza (Analytical review of the scientific literature). Izvestija vysshih uchebnyh zavedenij. Ural’skij region. 2016;(2):143–147. (In Russ.). EDN: https://elibrary.ru/wiryax.Kytikova OJu, Gvozdenko TA, Antonjuk MV, Novgorodceva TP. The role of nitric oxide in the pathophysiology and treatment of chronic obstructive pulmonary disease. Bulletin Physiology and Pathology of Respiration. 2019;1(71):105–111. (In Russ.). DOI: https://doi.org/10.12737/article_5c89ab4f8523c5.66345570.Kytikova OJu, Gvozdenko TA, Antonjuk MV, Novgorodceva TP. The role of nitric oxide in the pathophysiology and treatment of chronic obstructive pulmonary disease. Bulletin Physiology and Pathology of Respiration. 2019;1(71):105–111. (In Russ.). DOI: https://doi.org/10.12737/article_5c89ab4f8523c5.66345570.Kozina OV, Ogorodova LM. Formation and biological role of NO in allergic inflammation. Bulletin of Siberian Medicine. 2009;8(3):95–105. (In Russ.). DOI: https://doi.org/10.20538/1682-0363-2009-3-95-104.Kozina OV, Ogorodova LM. Formation and biological role of NO in allergic inflammation. Bulletin of Siberian Medicine. 2009;8(3):95–105. (In Russ.). DOI: https://doi.org/10.20538/1682-0363-2009-3-95-104.Kim IA, Nosulia EV, Orekhova KK. Pathogenetic value of nitric oxide in allergic rhinitis (A literature review). Russian Rhinology. 2015;23(2):68–71. (In Russ.). DOI: https://doi.org/10.17116/rosrino201523268-71.Kim IA, Nosulia EV, Orekhova KK. Pathogenetic value of nitric oxide in allergic rhinitis (A literature review). Russian Rhinology. 2015;23(2):68–71. (In Russ.). DOI: https://doi.org/10.17116/rosrino201523268-71.Bocharova NV, Novgorodceva TP. Levels of nitric oxide metabolites in the blood of patients with chronic respiratory diseases. Zdorov’e. Medicinskaja jekologija. Nauka. 2017;(4):27–31. (In Russ.). DOI: https://doi.org/10.5281/zenodo.835308.Bocharova NV, Novgorodceva TP. Levels of nitric oxide metabolites in the blood of patients with chronic respiratory diseases. Zdorov’e. Medicinskaja jekologija. Nauka. 2017;(4):27–31. (In Russ.). DOI: https://doi.org/10.5281/zenodo.835308.Nefedov IV, Shishimorov IN, Magnitskaya OV. Exhaled nitric oxide as a predictor of the effectiveness of basic therapy for bronchial asthma in children. Research Results in Biomedicine. 2020;6(2):238–248. (In Russ.). DOI: https://doi.org/10.18413/2658-6533-2020-6-2-0-8.Nefedov IV, Shishimorov IN, Magnitskaya OV. Exhaled nitric oxide as a predictor of the effectiveness of basic therapy for bronchial asthma in children. Research Results in Biomedicine. 2020;6(2):238–248. (In Russ.). DOI: https://doi.org/10.18413/2658-6533-2020-6-2-0-8.Edranov SS. The role of nitric oxide in damage and reparations mucous membrane maxillary sinus. Russian Journal of Dentistry. 2012;(6):38–42. (In Russ.). EDN: https://elibrary.ru/punbhx.Edranov SS. The role of nitric oxide in damage and reparations mucous membrane maxillary sinus. Russian Journal of Dentistry. 2012;(6):38–42. (In Russ.). EDN: https://elibrary.ru/punbhx.Motov VS, Bykov VV, Bykova AV, Vengerovskii AI. Anti-inflammatory and analgesic activity of an inducible NO synthase inhibitor in an experiment. Journal of Siberian Medical Sciences. 2022;6(1):106–115. (In Russ.). DOI: https://doi.org/10.31549/2542-1174-2022-6-1-106-115.Motov VS, Bykov VV, Bykova AV, Vengerovskii AI. Anti-inflammatory and analgesic activity of an inducible NO synthase inhibitor in an experiment. Journal of Siberian Medical Sciences. 2022;6(1):106–115. (In Russ.). DOI: https://doi.org/10.31549/2542-1174-2022-6-1-106-115.Bashkatova VG, Alekseeva EV, Nazarova GA, Sudakov SK. Influence of a nitric oxide synthase inhibitor on the learning and spatial memory of rats exposed to long perinatal administration of caffeine. Bulletin of Experimental Biology and Medicine. 2022;173(1):29–32. (In Russ.). DOI: https://doi.org/10.47056/0365-9615-2021-173-1-29-32.Bashkatova VG, Alekseeva EV, Nazarova GA, Sudakov SK. Influence of a nitric oxide synthase inhibitor on the learning and spatial memory of rats exposed to long perinatal administration of caffeine. Bulletin of Experimental Biology and Medicine. 2022;173(1):29–32. (In Russ.). DOI: https://doi.org/10.47056/0365-9615-2021-173-1-29-32.Shahmardanova SA, Gulevskaja ON, Seleckaja VV. Antioxidants: Classification, pharmacotherapeutic properties, use in practical medicine. Zhurnal fundamental’noj mediciny I biologii. 2016;(3):4–15. (In Russ.). EDN: https://elibrary.ru/xqsidl.Shahmardanova SA, Gulevskaja ON, Seleckaja VV. Antioxidants: Classification, pharmacotherapeutic properties, use in practical medicine. Zhurnal fundamental’noj mediciny I biologii. 2016;(3):4–15. (In Russ.). EDN: https://elibrary.ru/xqsidl.Berest IE. Macroscopic evaluation of nasal mucosal regeneration aſter trauma (Experimental study). Ural Medical Journal. 2023;22(4):69–76. (In Russ.). DOI: https://doi.org/10.52420/2071-5943-2023-22-4-69-76.Berest IE. Macroscopic evaluation of nasal mucosal regeneration aſter trauma (Experimental study). Ural Medical Journal. 2023;22(4):69–76. (In Russ.). DOI: https://doi.org/10.52420/2071-5943-2023-22-4-69-76.BerestIYe, Tananakina TP, Teleshova OV, Burgelo EV, Parinov RA, Koretsky AV. Evaluating the developed model of experimental rhinitisin laboratory rats: Pre-clinical experimental randomized study. Kuban Scientific Medical Bulletin. 2023;30(1):78–87. (In Russ.). DOI: https://doi.org/10.25207/1608-6228-2023-30-1-78-87.BerestIYe, Tananakina TP, Teleshova OV, Burgelo EV, Parinov RA, Koretsky AV. Evaluating the developed model of experimental rhinitisin laboratory rats: Pre-clinical experimental randomized study. Kuban Scientific Medical Bulletin. 2023;30(1):78–87. (In Russ.). DOI: https://doi.org/10.25207/1608-6228-2023-30-1-78-87.Ricciardolo FLM, Sterk PJ, Gaston B, Folkerts G. Nitric oxide in health and disease of the respiratory system. Physiological Reviews. 2004;84(3):731–765. DOI: https://doi.org/10.1152/physrev.00034.2003.Ricciardolo FLM, Sterk PJ, Gaston B, Folkerts G. Nitric oxide in health and disease of the respiratory system. Physiological Reviews. 2004;84(3):731–765. DOI: https://doi.org/10.1152/physrev.00034.2003.Ismagilov ShM, Giljalov MN, Ismagilov MF. Complex therapy of patients with rhinosinusitis, taking into account the characteristics of the vegetative status. Prakticheskaja medicina. 2016;(4–2):36–38. (In Russ.). Available from: https://clck.ru/3A65cS [Accessed: 19 December 2023].Ismagilov ShM, Giljalov MN, Ismagilov MF. Complex therapy of patients with rhinosinusitis, taking into account the characteristics of the vegetative status. Prakticheskaja medicina. 2016;(4–2):36–38. (In Russ.). Available from: https://clck.ru/3A65cS [Accessed: 19 December 2023].Maximov ML, Malykhina AI, Shikaleva AA. Time-proved pharmacotherapy: From mechanisms to clinical efficacy. RMJ. 2020;28(9):71–76. (In Russ.). EDN: https://elibrary.ru/ncnrqt.Maximov ML, Malykhina AI, Shikaleva AA. Time-proved pharmacotherapy: From mechanisms to clinical efficacy. RMJ. 2020;28(9):71–76. (In Russ.). EDN: https://elibrary.ru/ncnrqt.Nizamutdinova JeR, Anchikova LI, Slavin LE, ValeevaIH. Influence “Dimephosphone” on indicators of antioxidant system of the body, the content of nitrite ion in the blood serum of patients with diabetes mellitus type 2, complicating by the diabetic foot syndrome. Prakticheskaja medicina. 2010;(4). (In Russ.).Nizamutdinova JeR, Anchikova LI, Slavin LE, ValeevaIH. Influence “Dimephosphone” on indicators of antioxidant system of the body, the content of nitrite ion in the blood serum of patients with diabetes mellitus type 2, complicating by the diabetic foot syndrome. Prakticheskaja medicina. 2010;(4). (In Russ.).Bajke EV, Hyshiktuev BS, Svirskij RP. Efficacy of dimephosphone in patients with chronic purulent otitis media. Baikal Medical Journal. 2007;71(4):42–45. (In Russ.). EDN: https://elibrary.ru/pfbjdl.Bajke EV, Hyshiktuev BS, Svirskij RP. Efficacy of dimephosphone in patients with chronic purulent otitis media. Baikal Medical Journal. 2007;71(4):42–45. (In Russ.). EDN: https://elibrary.ru/pfbjdl.Popovich O, Stratu E, Koreckij Ja, Gikavyj V. Efficacy of NO synthase inhibitors in inflammation. Vestnik sovremennoj nauki. 2016;(10–1):104–108. (In Russ.). EDN: https://elibrary.ru/wzzlpl.Popovich O, Stratu E, Koreckij Ja, Gikavyj V. Efficacy of NO synthase inhibitors in inflammation. Vestnik sovremennoj nauki. 2016;(10–1):104–108. (In Russ.). EDN: https://elibrary.ru/wzzlpl.

The authors declare that there are no conflicts of interest present.