antibioticsАнтибиотики и ХимиотерапияAntibiot Khimioter = Antibiotics and Chemotherapy0235-2990ООО «Издательство ОКИ»10.37489/0235-2990-2023-68-1-2-57-68antibiotics-1004Research ArticleОБЗОРЫREVIEWSСукцинат и сукцинатдегидрогеназа как «точка опоры» в цикле Кребса при критических состоянияхSuccinate and succinate dehydrogenase as a «foothold» in the Krebs cycle in critical conditionshttps://orcid.org/0000-0002-6747-998XОрловЮ. П.OrlovYu. P.

Орлов Юрий Петрович — д. м. н., доцент, профессор кафедры анестезиологии и реаниматологии

ул. Ленина,12, г. Омск, 644099, Сибирский Федеральный округ, Омская область

Yurii P. Orlov — D. Sc. in Medicine, Associate Professor, Professor at the Department of Anesthesiology and Intensive Care

12 Lenina st., Omsk, 644099

orlov-up@mail.ruhttps://orcid.org/0000-0002-0033-783XБутровА. В.ButrovA. V.

Бутров Андрей Валерьевич — д. м. н., профессор врач-анестезиолог-реаниматолог; заведующий кафедрой анестезиологии и реаниматологии

Москва

Andrey V. Butrov — D. Sc. in Medicine, Professor, anesthesiologist-resuscitator; Head of the Department of Anesthesiology and Intensive Care

Moscow

https://orcid.org/0000-0002-9976-8903СвиридовС. В.SviridovS. V.

Свиридов Сергей Викторович — д. м. н., профессор заведующий кафедрой анестезиологии, реаниматологии и интенсивной терапии ЛФ

Москва

Sergey V. Sviridov — D. Sc. in Medicine, Professor, Head of the Department of Anesthesiology, Resuscitation, and Intensive Care

Moscow

https://orcid.org/0000-0001-6504-8169АфанасьевВ. В.AfanasievV. V.

Афанасьев Василий Владимирович — д. м. н. врач-токсиколог, профессор кафедры неотложной медицины

Санкт-Петербург

Vasily V. Afanasiev — D. Sc. in Medicine, Toxicologist, Professor, Department of Emergency Medicine

St. Petersburg

https://orcid.org/0000-0002-7648-2208КондратьевА. Н.KondratievA. N.

Кондратьев Анатолий Николаевич — д. м. н., профессор, заслуженный врач Российской Федерации, заведующий НИЛ нейропротекции и нейрометаболических нарушений Российского научно-исследовательского нейрохирургического института им. профессора А. Л. Поленова

Санкт-Петербург

Anatoly N. Kondratiev — D. Sc. in Medicine, Professor, Honored doctor of the Russian Federation, Head of the Research Laboratory of Neuroprotection and Neurometabolic Disorders, Polenov Neurosurgical Institute

St. Petersburg

https://orcid.org/0000-0001-7527-7707ЦенциперЛ. М.TsentsiperL. M.

Ценципер Любовь Марковна — д. м. н., профессор кафедры анестезиологии и реаниматологии с клиникой ИМО; ведущий научный сотрудник НИЛ нейропротекции и нейрометаболических нарушений Российского научно-исследовательского нейрохирургического института имени профессора А. Л. Поленова

Санкт-Петербург

Lubov M. Tsentsiper — Ph. D. in Medicine, Associate Professor of the Department of Anesthesiology and Resuscitation, Leading researcher of the Research Laboratory of Neuroprotection and Neurometabolic Disorders, Polenov Neurosurgical Institute

St. Petersburg

https://orcid.org/0000-0002-0495-902XГовороваН. В.GovorovaN. V.

Говорова Наталья Валерьевна — д. м. н., профессор, заведующая кафедрой анестезиологии и раниматологии

Омск

Nataly V. Govorova — D. Sc. in Medicine, Professor, Head of the Department of Anesthesiology and Intensive Care

Omsk

https://orcid.org/0000-0001-9761-5957КондратьевА. И.KondratievA. I.

Кондратьев Аркадий Иванович — к. м. н., доцент кафедры анестезиологии и реаниматологии

Омск

Arkady I. Kondratiev — Ph. D. in Medicine, Associate Professor of the Department of Anesthesiology and Intensive Care

Omsk

https://orcid.org/0000-0002-6479-7915БайтугаеваГ. А.BaytugaevaG. A.

Байтугаева Галина Абукановна — к. м. н., доцент кафедры анестезиологии и реаниматологии

Омск

Galina A. Baytugaeva — Ph. D. in Medicine, Associate Professor of the Department of Anesthesiology and Resuscitation

Omsk

https://orcid.org/0000-0002-2811-6051КакуляЕ. Н.KakulyaE. N.

Какуля Евгений Николаевич — к. м. н., ассистент кафедры анестезиологии и реаниматологии

Омск

Evgeny N. Kakulya — Ph. D. in Medicine, Assistant of the Department of Anesthesiology and Intensive Care

Omsk

ФГБОУ ВО «Омский государственный медицинский университет» Минздрава РоссииРоссияOmsk State Medical UniversityRussian FederationФГАОУ ВО «Российский университет дружбы народов»РоссияRUDN UniversityRussian FederationФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н. И. Пирогова» Минздрава РоссииРоссияPirogov Russian National Research Medical UniversityRussian FederationФГБОУ ВО «Северо-Западный государственный медицинский университет им. И. И. Мечникова» Минздрава РоссииРоссияNorth-Western State Medical University named after I. I. MechnikovRussian FederationФГБУ «Национальный медицинский исследовательский центр им. В. А. Алмазова» Минздрава РоссииРоссияAlmazov National Medical Research CenterRussian Federation202330042023681-25768Copyright © Орлов Ю.П., Бутров А.В., Свиридов С.В., Афанасьев В.В., Кондратьев А.Н., Ценципер Л.М., Говорова Н.В., Кондратьев А.И., Байтугаева Г.А., Какуля Е.Н., 20232023Орлов Ю.П., Бутров А.В., Свиридов С.В., Афанасьев В.В., Кондратьев А.Н., Ценципер Л.М., Говорова Н.В., Кондратьев А.И., Байтугаева Г.А., Какуля Е.Н.Orlov Y.P., Butrov A.V., Sviridov S.V., Afanasiev V.V., Kondratiev A.N., Tsentsiper L.M., Govorova N.V., Kondratiev A.I., Baytugaeva G.A., Kakulya E.N.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.antibiotics-chemotherapy.ru/jour/article/view/1004

Цель. Поиск и представление данных экспериментальных и клинических исследований, отражающих центральную роль сукцината и сукцинатдегидрогеназы в регуляции механизмов адаптации при критических состояниях. Материал и методы. Поиск источников литературы проводился с использованием электронных ресурсов российской научной электронной библиотеки eLIBRARY.ru, где использовались следующие ключевые слова «цикл Кребса, сукцинат, сукцинатдегидрогеназа, критические состояния» и в англоязычной текстовой базе медицинских и биологических публикаций по медицинским наукам PUBMED, где были использованы аналогичные ключевые слова «Krebs cycle, succinate, succinate dehydrogenase, critical conditions». Результаты. С учётом данных, представленных в обзоре, можно констатировать, что комплекс сукцинат и сукцинатдегидрогеназа является центральным звеном цикла Кребса и главной структурой антигипоксического ансамбля всех клеток организма в период адаптации при критических состояниях. Заключение. Данные экспериментальных и клинических исследований, отражающих центральную роль сукцината и сукцинатдегидрогеназы не только в механизмах адаптации к гипоксии, а также в регуляции воспаления, термогенеза, расстройств гемостаза, кислотно-основного состояния, обмена электролитов, сосудистого тонуса и трофики тканей кишечника, а также в иммунологических реакциях организма, позволяют рассматривать субстрат и фермент как центральное звено цикла Кребса и главной структурой антигипоксического ансамбля всех клеток организма. Приведённые в обзоре данные открывают новые перспективы использования сукцинатов при критических состояниях.

Purpose. Search and presentation of data from experimental and clinical studies reflecting the central role of succinate and succinate dehydrogenase in the regulation of adaptation mechanisms in critical conditions. Material and methods. The search for literature sources was carried out using the electronic resources of the Russian scientific electronic library eLIBRARY.ru, with the use of the following keywords: «Krebs cycle, succinate, succinate dehydrogenase, critical conditions», as well as in the English-language text database of medical and biological publications on medical sciences PUBMED, where similar keywords «Krebs cycle, succinate, succinate dehydrogenase, critical conditions» were used. Results. Taking into account the data presented in the review, it can be stated that the complex of succinate and succinate dehydrogenase is the central link in the Krebs cycle and the main structure of the antihypoxic ensemble of all body cells during the adaptation period under critical conditions. Conclusion. The data of experimental and clinical studies reflecting the central role of succinate and succinate dehydrogenase not only in the mechanisms of adaptation to hypoxia, but also in the regulation of inflammation, thermogenesis, hemostasis disorders, acid-base state, electrolyte metabolism, vascular tone and trophism of intestinal tissues, as well as in immunological reactions of the body, allow us to consider the substrate and enzyme as the central link of the Krebs cycle and the main structure of the antihypoxic ensemble of all body cells. The data presented in the review open up new prospects for the use of succinates in critical conditions.

цикл Кребсасукцинатсукцинатдегидрогеназакритические состоянияKrebs cyclesuccinatesuccinate dehydrogenasecritical conditionsReferencesThunberg T. The Hydrogen-activating enzymes of the cells. The Quarterly Review of Biology. 1930; 5 (3): 318–347. doi: https://doi.org/10.1086/394361.Thunberg T. The Hydrogen-activating enzymes of the cells. The Quarterly Review of Biology. 1930; 5 (3): 318–347. doi: https://doi.org/10.1086/394361.Rall J.A. Generation of life in a test tube: Albert Szent-Gyorgyi, Bruno Straub, and the discovery of actin. Adv Physiol Educ. 2018 Jun 1; 42 (2): 277–288. doi: 10.1152/advan.00189.2017.Rall J.A. Generation of life in a test tube: Albert Szent-Gyorgyi, Bruno Straub, and the discovery of actin. Adv Physiol Educ. 2018 Jun 1; 42 (2): 277–288. doi: 10.1152/advan.00189.2017.Krebs H.A. Some aspects of the energy transformation in living matter. Br Med Bull. 1953; 9 (2): 97–104. doi: 10.1093/oxfordjournals.bmb.a074347.Krebs H.A. Some aspects of the energy transformation in living matter. Br Med Bull. 1953; 9 (2): 97–104. doi: 10.1093/oxfordjournals.bmb.a074347.Krebs H.A. Die energieliefernden Reaktionen des Stoffwechsels [Energy furnishing reactions of metabolism]. Klin Wochenschr. 1957 Mar 1; 35 (5): 209–13. German. doi: 10.1007/BF01482767.Krebs H.A. Die energieliefernden Reaktionen des Stoffwechsels Energy furnishing reactions of metabolism. Klin Wochenschr. 1957 Mar 1; 35 (5): 209–13. German. doi: 10.1007/BF01482767.Lee I., Hüttemann M. Energy crisis: the role of oxidative phosphorylation in acute inflammation and sepsis. Biochim Biophys Acta. 2014 Sep; 1842 (9): 1579–86. doi: 10.1016/j.bbadis.2014.05.031.Lee I., Hüttemann M. Energy crisis: the role of oxidative phosphorylation in acute inflammation and sepsis. Biochim Biophys Acta. 2014 Sep; 1842 (9): 1579–86. doi: 10.1016/j.bbadis.2014.05.031.Ackrell B.A. Progress in understanding structure-function relationships in respiratory chain complex II. FEBS Lett. 2000 Jan 21; 466 (1): 1–5. doi: 10.1016/s0014-5793(99)01749-4.Ackrell B.A. Progress in understanding structure-function relationships in respiratory chain complex II. FEBS Lett. 2000 Jan 21; 466 (1): 1–5. doi: 10.1016/s0014-5793(99)01749-4.Moosavi B., Berry E.A., Zhu X.L., Yang W.C., Yang G.F. The assembly of succinate dehydrogenase: a key enzyme in bioenergetics. Cell Mol Life Sci. 2019 Oct; 76 (20): 4023–4042. doi: 10.1007/s00018-019-03200-7.Moosavi B., Berry E.A., Zhu X.L., Yang W.C., Yang G.F. The assembly of succinate dehydrogenase: a key enzyme in bioenergetics. Cell Mol Life Sci. 2019 Oct; 76 (20): 4023–4042. doi: 10.1007/s00018-019-03200-7.Bénit P., Goncalves J., El Khoury R., Rak M., Favier J., Gimenez-Roqueplo A.P., Rustin P. Succinate dehydrogenase, succinate, and superoxides: a genetic, epigenetic, metabolic, environmental explosive crossroad. Biomedicines. 2022 Jul 25; 10 (8): 1788. doi: 10.3390/biomedicines10081788.Bénit P., Goncalves J., El Khoury R., Rak M., Favier J., Gimenez-Roqueplo A.P., Rustin P. Succinate dehydrogenase, succinate, and superoxides: a genetic, epigenetic, metabolic, environmental explosive crossroad. Biomedicines. 2022 Jul 25; 10 (8): 1788. doi: 10.3390/biomedicines10081788.Protasoni M., Zeviani M. Mitochondrial structure and bioenergetics in normal and disease conditions. Int J Mol Sci. 2021 Jan 8; 22 (2): 586. doi: 10.3390/ijms22020586.Protasoni M., Zeviani M. Mitochondrial structure and bioenergetics in normal and disease conditions. Int J Mol Sci. 2021 Jan 8; 22 (2): 586. doi: 10.3390/ijms22020586.Rutter J.W.D., Schiffman J.D. Succinate dehydrogenase — Assembly, regulation and role in human disease. Mitochondrion. 2010; 10: 393–401. doi: 10.1016/j.mito.2010.03.001.Rutter J.W.D., Schiffman J.D. Succinate dehydrogenase — Assembly, regulation and role in human disease. Mitochondrion. 2010; 10: 393–401. doi: 10.1016/j.mito.2010.03.001.Tretter L., Patocs A., Chinopoulos C. Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis. Biochimica et Biophysica Acta. 2016; 1857 (8): 1086–1101. doi: 10.1016/j.bbabio.2016.03.012.Tretter L., Patocs A., Chinopoulos C. Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis. Biochimica et Biophysica Acta. 2016; 1857 (8): 1086–1101. doi: 10.1016/j.bbabio.2016.03.012.Chance B., Williams G.R. A method for the localization of sites for oxidative phosphorylation. Nature. 1955 Aug 6; 176 (4475): 250–254.Chance B., Williams G.R. A method for the localization of sites for oxidative phosphorylation. Nature. 1955 Aug 6; 176 (4475): 250–254.Chance B., Williams G.R. Respiratory enzymes in oxidative phosphorylation. VI. The effects of adenosine diphosphate on azide-treated mitochondria. J Biol Chem. 1956 Jul; 221 (1): 477–489.Chance B., Williams G.R. Respiratory enzymes in oxidative phosphorylation. VI. The effects of adenosine diphosphate on azide-treated mitochondria. J Biol Chem. 1956 Jul; 221 (1): 477–489.Chance B., Hollunger G. The interaction of energy and electron transfer reactions in mitochondria. I. General properties and nature of the products of succinate-linked reduction of pyridine nucleotide. J Biol Chem. 1961 May; 236: 1534–1543.Chance B., Hollunger G. The interaction of energy and electron transfer reactions in mitochondria. I. General properties and nature of the products of succinate-linked reduction of pyridine nucleotide. J Biol Chem. 1961 May; 236: 1534–1543.El-Hattab A.W., Adesina A.M., Jones J., Scaglia F. MELAS syndrome: clinical manifestations, pathogenesis, and treatment options. Mol Genet Metab. 2015 Sep-Oct; 116 (1–2): 4–12. doi: 10.1016/j.ymgme.2015.06.004.El-Hattab A.W., Adesina A.M., Jones J., Scaglia F. MELAS syndrome: clinical manifestations, pathogenesis, and treatment options. Mol Genet Metab. 2015 Sep-Oct; 116 (1–2): 4–12. doi: 10.1016/j.ymgme.2015.06.004.Granger D.N., Kvietys P.R. Reperfusion injury and reactive oxygen species: The evolution of a concept. Redox Biol. 2015 Dec; 6: 524–551. doi: 10.1016/j.redox.2015.08.020.Granger D.N., Kvietys P.R. Reperfusion injury and reactive oxygen species: The evolution of a concept. Redox Biol. 2015 Dec; 6: 524–551. doi: 10.1016/j.redox.2015.08.020.Handbook of flavoproteins: volume 2: Complex flavoproteins, dehydrogenases and physical methods / Russ Hille, Susan Miller, Bruce Palfey (eds.). Berlin: Walter de Gruyter & Co. 2013; 2: 141–436.Handbook of flavoproteins: volume 2: Complex flavoproteins, dehydrogenases and physical methods / Russ Hille, Susan Miller, Bruce Palfey (eds.). Berlin: Walter de Gruyter & Co. 2013; 2: 141–436.Ousaka D., Nishibori M. A new approach to combat the sepsis including COVID-19 by accelerating detoxification of hemolysis-related DAMPs. Nihon Yakurigaku Zasshi. 2022; 157 (6): 422–425. Japanese. doi: 10.1254/fpj.22073.Ousaka D., Nishibori M. A new approach to combat the sepsis including COVID-19 by accelerating detoxification of hemolysis-related DAMPs. Nihon Yakurigaku Zasshi. 2022; 157 (6): 422–425. Japanese. doi: 10.1254/fpj.22073.Hirota K. Basic biology of hypoxic responses mediated by the transcription factor HIFs and its implication for medicine. Biomedicines. 2020 Feb 13; 8 (2): 32. doi: 10.3390/biomedicines8020032.Hirota K. Basic biology of hypoxic responses mediated by the transcription factor HIFs and its implication for medicine. Biomedicines. 2020 Feb 13; 8 (2): 32. doi: 10.3390/biomedicines8020032.Лукьянова Л. Д. Сигнальные механизмы гипоксии. М.: Российская академия наук, 2019; 215. ISBN 978-5-907036-45-1. EDN ZXWRHB.Luk'yanova L. D. Signal'nye mekhanizmy gipoksii. Moscow: Rossijskaya Akademiya Nauk, 2019; 215. ISBN 978-5-907036-45-1. EDN ZXWRHB. (in Russian)Ariza A.C., Deen P.M., Robben J.H. The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions. Front Endocrinol (Lausanne). 2012 Feb 16; 3: 22. doi: 10.3389/fendo.2012.00022.Ariza A.C., Deen P.M., Robben J.H. The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions. Front Endocrinol (Lausanne). 2012 Feb 16; 3: 22. doi: 10.3389/fendo.2012.00022.Semenza G.L. Hypoxia-inducible factors in physiology and medicine. Cell. 2012; 148: 399–408.Semenza G.L. Hypoxia-inducible factors in physiology and medicine. Cell. 2012; 148: 399–408.Weinberg J.M., Venkatachalam M.A., Roeser N.F., Nissim I. Mitochondrial dysfunction during hypoxia/reoxygenation and its correction by anaerobic metabolism of citric acid cycle intermediates. Proc Natl Acad Sci U S A. 2000 Mar 14; 97 (6): 2826–31. doi: 10.1073/pnas.97.6.2826.Weinberg J.M., Venkatachalam M.A., Roeser N.F., Nissim I. Mitochondrial dysfunction during hypoxia/reoxygenation and its correction by anaerobic metabolism of citric acid cycle intermediates. Proc Natl Acad Sci U S A. 2000 Mar 14; 97 (6): 2826–31. doi: 10.1073/pnas.97.6.2826.Lukyanova L.D., Kirova Y.I. Mitochondria-controlled signaling mechanisms of brain protection in hypoxia. Front Neurosci. 2015 Oct 1; 9: 320. doi: 10.3389/fnins.2015.00320.Lukyanova L.D., Kirova Y.I. Mitochondria-controlled signaling mechanisms of brain protection in hypoxia. Front Neurosci. 2015 Oct 1; 9: 320. doi: 10.3389/fnins.2015.00320.Fedotcheva N.I., Sokolov A.P., Kondrashova M.N. Nonezymatic formation of succinate in mitochondria under oxidative stress. Free Radic Biol Med. 2006 Jul 1; 41 (1): 56–64. doi: 10.1016/j.freeradbiomed.2006.02.012.Fedotcheva N.I., Sokolov A.P., Kondrashova M.N. Nonezymatic formation of succinate in mitochondria under oxidative stress. Free Radic Biol Med. 2006 Jul 1; 41 (1): 56–64. doi: 10.1016/j.freeradbiomed.2006.02.012.Lukyanova L., Germanova E., Khmil N., Pavlik L., Mikheeva I., Shigaeva M., Mironova G. Signaling role of mitochondrial enzymes and ultrastructure in the formation of molecular mechanisms of adaptation to hypoxia. Int J Mol Sci. 2021 Aug 11; 22 (16): 8636. doi: 10.3390/ijms22168636.Lukyanova L., Germanova E., Khmil N., Pavlik L., Mikheeva I., Shigaeva M., Mironova G. Signaling role of mitochondrial enzymes and ultrastructure in the formation of molecular mechanisms of adaptation to hypoxia. Int J Mol Sci. 2021 Aug 11; 22 (16): 8636. doi: 10.3390/ijms22168636.Маевский Е.И., Гришина Е.В., Розенфельд А.С., Зиакун А.М., Верещагина В.М., Кондрашова М.Н. Анаэробное образование сукцината и облегчение его окисления — возможные механизмы адаптации клетки к кислородному голоданию. Биофизика. 2000; 45 (3): 509–513. PMID: 10872064.Maevskij E.I., Grishina E.V., Rozenfel'd A.S., Ziakun A.M., Vereshchagina V.M., Kondrashova M.N. Anaerobnoe obrazovanie suktsinata i oblegchenie ego okisleniya — vozmozhnye mekhanizmy adaptatsii kletki k kislorodnomu golodanijyu. Biofizika. 2000; 45 (3): 509–513. PMID: 10872064. (in Russian)Маевский Е.И., Розенфельд А.С., Песков А.Б., Кондрашова М.Н. Сигнальное симпатическое действие сукцината в экспериментальных и клинических исследованиях; Материалы 14-й Европейской конференции по биоэнергетике. Краткие доклады. 2006. М.: Россия. 22–27 июля 2006; 536–537.Maevskij E.I., Rozenfel'd A.S., Peskov A.B., Kondrashova M.N. Signal'noe simpaticheskoe dejstvie suktsinata v eksperimental'nykh i klinicheskikh issledovaniyakh; Materialy 14-j Evropejskoj konferentsii po bioenergetike. Kratkie Doklady. 2006. M.: Rossiya. 22–27 ijyulya 2006; 536–537. (in Russian)Solberg R., Enot D., Deigner H.P., Koal T., Scholl-Bürgi S., Saugstad O.D., Keller M. Metabolomic analyses of plasma reveals new insights into asphyxia and resuscitation in pigs. PLoS One. 2010 Mar 9; 5 (3): e9606. doi: 10.1371/journal.pone.0009606.Solberg R., Enot D., Deigner H.P., Koal T., Scholl-Bürgi S., Saugstad O.D., Keller M. Metabolomic analyses of plasma reveals new insights into asphyxia and resuscitation in pigs. PLoS One. 2010 Mar 9; 5 (3): e9606. doi: 10.1371/journal.pone.0009606.Preiser J.-C. Oxidative stress. J Parenter Enteral Nutr. 2012; 36 (2): 147–154. doi: 10.1177/0148607111434963.Preiser J.-C. Oxidative stress. J Parenter Enteral Nutr. 2012; 36 (2): 147–154. doi: 10.1177/0148607111434963.Galley H. F. Oxidative stress and mitochondrial dysfunction in sepsis. Br J Anaesth. 2011; 107 (1): 57–64. doi: 10.1093/bja/aer093.Galley H. F. Oxidative stress and mitochondrial dysfunction in sepsis. Br J Anaesth. 2011; 107 (1): 57–64. doi: 10.1093/bja/aer093.Protti A., Carré J., Frost M. T. et al. Succinate recovers mitochondrial oxygen consumption in septic rat skeletal muscle. Crit Care Med. 2007; 35 (9): 2150–2155. doi: 10.1097/01.ccm.0000281448.00095.4d.Protti A., Carré J., Frost M. T. et al. Succinate recovers mitochondrial oxygen consumption in septic rat skeletal muscle. Crit Care Med. 2007; 35 (9): 2150–2155. doi: 10.1097/01.ccm.0000281448.00095.4d.Ferreira F., Ladrière L., Vincent J. L., Malaisse W. Prolongation of survival time by infusion of succinic acid dimethyl ester in a caecal ligation and perforation model of sepsis. Hormone and Metabolic Research. 2000; 32 (8): 335–336. doi: 10.1055/s-2007-978647.Ferreira F., Ladrière L., Vincent J. L., Malaisse W. Prolongation of survival time by infusion of succinic acid dimethyl ester in a caecal ligation and perforation model of sepsis. Hormone and Metabolic Research. 2000; 32 (8): 335–336. doi: 10.1055/s-2007-978647.Malaisse W. J., Nadi A. B., Ladriere L., Zhang T. M. Protective effects of succinic acid dimethyl ester infusion in experimental endotoxemia. Nutrition. 1997; 13 (4): 330–341.Malaisse W. J., Nadi A. B., Ladriere L., Zhang T. M. Protective effects of succinic acid dimethyl ester infusion in experimental endotoxemia. Nutrition. 1997; 13 (4): 330–341.Barrett R.H. Sodium succinate; clinical use in respiratory depression. Curr Res Anesth Analg. 1948 Nov-Dec; 27 (6): 326–335. PMID: 18893455.Barrett R.H. Sodium succinate; clinical use in respiratory depression. Curr Res Anesth Analg. 1948 Nov-Dec; 27 (6): 326–335. PMID: 18893455.Olletti M. Esperienze cliniche sul trattamento dell'asma infantile con acido succinico. Clinical experience in the treatment of infantile asthma with succinic acid. Acta Paediatr Lat. 1951 May–Jun; 4 (3): 265–267.Olletti M. Esperienze cliniche sul trattamento dell'asma infantile con acido succinico. Clinical experience in the treatment of infantile asthma with succinic acid. Acta Paediatr Lat. 1951 May–Jun; 4 (3): 265–267.Goupil A., Corolleur J.R., Warnery M., Fargepallet G. Etude spirographique de l'action de l'acide succinique chez 117 malades. Spirographic study on the action of succinic acid in 117 patients. Poulmon. 1952 Aug–Sep; 8 (7): 613–624.Goupil A., Corolleur J.R., Warnery M., Fargepallet G. Etude spirographique de l'action de l'acide succinique chez 117 malades. Spirographic study on the action of succinic acid in 117 patients. Poulmon. 1952 Aug–Sep; 8 (7): 613–624.Jenkins L.C., Graves H.B. An appraisal of the present treatment of barbiturate poisoning. Can Anaesth Soc J. 1958 Jan; 5 (1): 41–54. doi: 10.1007/BF03015576. PMID: 13489525.Jenkins L.C., Graves H.B. An appraisal of the present treatment of barbiturate poisoning. Can Anaesth Soc J. 1958 Jan; 5 (1): 41–54. doi: 10.1007/BF03015576. PMID: 13489525.Aird R.B. Succinate therapy in multiple sclerosis. Neurology. 1951 MayJun; 1 (3): 219–227. doi: 10.1212/wnl.1.5.219. PMID: 14833533.Aird R.B. Succinate therapy in multiple sclerosis. Neurology. 1951 MayJun; 1 (3): 219–227. doi: 10.1212/wnl.1.5.219. PMID: 14833533.Chapela S.P., Burgos I., Congost C., Canzonieri R., Muryan A., Alonso M., Stella C.A. Parenteral succinate reduces systemic ROS production in septic rats, but it does not reduce creatinine levels. Oxid Med Cell Longev. 2018 Nov 6; 2018: 1928945. doi: 10.1155/2018/1928945.Chapela S.P., Burgos I., Congost C., Canzonieri R., Muryan A., Alonso M., Stella C.A. Parenteral succinate reduces systemic ROS production in septic rats, but it does not reduce creatinine levels. Oxid Med Cell Longev. 2018 Nov 6; 2018: 1928945. doi: 10.1155/2018/1928945.Van Wyngene L., Vandewalle J., Libert C. Reprogramming of basic metabolic pathways in microbial sepsis: therapeutic targets at last? EMBO Mol Med. 2018; 10 (8): e8712). doi: 10.15252/emmm.201708712.Van Wyngene L., Vandewalle J., Libert C. Reprogramming of basic metabolic pathways in microbial sepsis: therapeutic targets at last? EMBO Mol Med. 2018; 10 (8): e8712). doi: 10.15252/emmm.201708712.Lorente L., Martín M. M., López-Gallardo E. et al. Decrease of oxidative phosphorylation system function in severe septic patients. J Crit Care. 2015; 30 (5): 935–939. doi: 10.1016/j.jcrc.2015.05.031.Lorente L., Martín M. M., López-Gallardo E. et al. Decrease of oxidative phosphorylation system function in severe septic patients. J Crit Care. 2015; 30 (5): 935–939. doi: 10.1016/j.jcrc.2015.05.031.Brealey D., Brand M., Hargreaves I. et al. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet. 2002; 360 (9328): 219–223. doi: 10.1016/S0140-6736(02)09459-X.Brealey D., Brand M., Hargreaves I. et al. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet. 2002; 360 (9328): 219–223. doi: 10.1016/S0140-6736(02)09459-X.Fink M.P. Bench-to-bedside review: Cytopathic hypoxia. Crit Care. 2002; 6: 491–499. doi: 10.1186/cc1824.Fink M.P. Bench-to-bedside review: Cytopathic hypoxia. Crit Care. 2002; 6: 491–499. doi: 10.1186/cc1824.Choi I., Son H., Baek J.H. Tricarboxylic acid (TCA) cycle intermediates: regulators of immune responses. Life (Basel). 2021 Jan 19; 11 (1): 69. doi: 10.3390/life11010069.Choi I., Son H., Baek J.H. Tricarboxylic acid (TCA) cycle intermediates: regulators of immune responses. Life (Basel). 2021 Jan 19; 11 (1): 69. doi: 10.3390/life11010069.Li X., Mao M., Zhang Y., Yu K., Zhu W. Succinate Modulates Intestinal Barrier Function and Inflammation Response in Pigs. Biomolecules. 2019; 9: 486. doi: 10.3390/biom9090486.Li X., Mao M., Zhang Y., Yu K., Zhu W. Succinate Modulates Intestinal Barrier Function and Inflammation Response in Pigs. Biomolecules. 2019; 9: 486. doi: 10.3390/biom9090486.Ciceri F., Beretta L., Scandroglio A.M., Colombo S., Landoni G., Ruggeri A., Peccatori J., D'Angelo A., De Cobelli F., Rovere-Querini P., Tresoldi M., Dagna L., Zangrillo A. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis. Crit Care Resusc. 2020 Apr 15; 22 (2): 95–97.Ciceri F., Beretta L., Scandroglio A.M., Colombo S., Landoni G., Ruggeri A., Peccatori J., D'Angelo A., De Cobelli F., Rovere-Querini P., Tresoldi M., Dagna L., Zangrillo A. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis. Crit Care Resusc. 2020 Apr 15; 22 (2): 95–97.Kulkarni P.P., Tiwari A., Singh N., Gautam D., Sonkar V.K., Agarwal V., Dash D. Aerobic glycolysis fuels platelet activation: small-molecule modulators of platelet metabolism as anti-thrombotic agents. Haematologica. 2019 Apr; 104 (4): 806–818. doi: 10.3324/haematol.2018.205724.Kulkarni P.P., Tiwari A., Singh N., Gautam D., Sonkar V.K., Agarwal V., Dash D. Aerobic glycolysis fuels platelet activation: small-molecule modulators of platelet metabolism as anti-thrombotic agents. Haematologica. 2019 Apr; 104 (4): 806–818. doi: 10.3324/haematol.2018.205724.Симутис И.С, Бояринов Г.А., Юрьев М.Ю., Петровский Д.С., Коваленко А.Л., Сапожников К.В. Первый опыт применения меглюмина натрия сукцината в коррекции COVID-19-ассоциированной коагулопатии. Общая реаниматология. 2021; 17 (3): 50–64. https://doi.org/10.15360/1813-9779-2021-3-5.Simutis I.S, Boyarinov G.A., Jyur'ev M.Jyu., Petrovskij D.S., Kovalenko A.L., Sapozhnikov K.V. Pervyj opyt primeneniya megljyumina natriya suktsinata v korrektsii COVID-19-assotsiirovannoj koagulopatii. Obshchaya Reanimatologiya. 2021; 17 (3): 50–64. https://doi.org/ 10.15360/1813-9779-2021-3-5. (in Russian)Камчатнов П.Р., Ханмурзаева С.Б., Чугунов А.В., Ханмурзаева Н.Б. Неврологические аспекты постковидного синдрома. Терапия. 2022; 3 (55): 144–152.Kamchatnov P.R., Khanmurzaeva S.B., Chugunov A.V., Khanmurzaeva N.B. Nevrologicheskie Aspekty Postkovidnogo Sindroma. Terapiya. 2022; 3 (55): 144–152. (in Russian)Drakesmith H., Prentice A. Viral infection and iron metabolism. Nat Rev Microbiol. 2008; 6 (7): 541–552. doi: 10.1038/nrmicro1930.Drakesmith H., Prentice A. Viral infection and iron metabolism. Nat Rev Microbiol. 2008; 6 (7): 541–552. doi: 10.1038/nrmicro1930.Liu W., Zhang S. , Nekhai S., Liu S. Depriving iron supply to the virus represents a promising adjuvant therapeutic against viral survival. Curr Clin Microbiol Rep. 2020; 7 (2): 20: 1–7. doi: 10.1007/s40588-020-00140-w.Liu W., Zhang S. , Nekhai S., Liu S. Depriving iron supply to the virus represents a promising adjuvant therapeutic against viral survival. Curr Clin Microbiol Rep. 2020; 7 (2): 20: 1–7. doi: 10.1007/s40588-020-00140-w.Guillon A., Brea-Diakite D., Cezard A., Wacquiez A., Baranek T., Bourgeais J. et al. Host succinate inhibits influenza virus infection through succinylation and nuclear retention of the viral nucleoprotein. EMBO J. 2022 Jun 14; 41 (12): e108306. doi: 10.15252/embj.2021108306.Guillon A., Brea-Diakite D., Cezard A., Wacquiez A., Baranek T., Bourgeais J. et al. Host succinate inhibits influenza virus infection through succinylation and nuclear retention of the viral nucleoprotein. EMBO J. 2022 Jun 14; 41 (12): e108306. doi: 10.15252/embj.2021108306.Иванова М. И., Щеглова Ю. М., Иванов В. М. и др. Применение реамберина при комплексной амбулаторной реабилитации больных, перенесших пневмонию, обусловленную SARS-CoV-2. Экспериментальная и клиническая фармакология. 2022; 85: (5): 15–19. doi: https://doi.org/10.30906/0869-2092-2022-85-5-15-19.Ivanova M. I., Shcheglova Jyu. M., Ivanov V. M. i dr. Primenenie reamberina pri kompleksnoj ambulatornoj reabilitatsii bol'nykh, perenesshikh pnevmonijyu, obuslovlennujyu SARS-CoV-2. Eksperimental'naya i Klinicheskaya Farmakologiya. 2022; 85: (5): 15–19. doi: https://doi.org/10.30906/0869-2092-2022-85-5-15-19. (in Russian)Яковлев А. Ю., Певнев А. А., Дудорова М. В. и др. Метаболическая терапия и её влияние на респираторную функцию лёгких у пациентов с тяжёлым течением COVID-19. Казанский медицинский журнал. 2022; 103 (3): 364–372. doi: https://doi.org/10.17816/KMJ2022-364.Yakovlev A. Jyu., Pevnev A. A., Dudorova M. V. i dr. Metabolicheskaya terapiya i ee vliyanie na respiratornujyu funktsijyu legkikh u patsientov s tyazhelym techeniem COVID-19. Kazanskij Meditsinskij Zhurnal. 2022; 103 (3): 364–372. doi: https://doi.org/10.17816/KMJ2022-364. (in Russian)Шаповалов К. Г., Цыденпилов Г. А., Лукьянов С. А. и др. Перспективы применения сукцинатов при тяжёлом течении новой коронавирусной инфекции. Экспериментальная и клиническая фармакология. 2020; 83 (10): 40–43. doi: https://doi.org/10.30906/0869-2092-2020-83-10-40-43.Shapovalov K. G., Tsydenpilov G. A., Luk'yanov S. A. i dr. Perspektivy primeneniya suktsinatov pri tyazhelom techenii novoj koronavirusnoj infektsii. Eksperimental'naya i Klinicheskaya Farmakologiya. 2020; 83 (10): 40–43. doi: https://doi.org/10.30906/0869-2092-2020-83-10-40-43. (in Russian)Трухан Д.И., Давыдов Е.Л. Лекарственные поражения печени: возможности полиионного сукцинат метионинового комплекса во время пандемии новой коронавирусной инфекции (COVID-19). Медицинский совет. 2021; 15: 110–121. https://doi.org/10.21518/2079-701X-2021-15-110-121.Trukhan D.I., Davydov E.L. Lekarstvennye porazheniya pecheni: vozmozhnosti poliionnogo suktsinat metioninovogo kompleksa vo vremya pandemii novoj koronavirusnoj infektsii (COVID-19). Meditsinskij Sovet. 2021; 15: 110–121. https://doi.org/10.21518/2079-701X-2021-15-110-121. (in Russian)Vohwinkel C.U., Coit E.J., Burns N., Elajaili H., Hernandez-Saavedra D., Yuan X. et al. Targeting alveolar-specific succinate dehydrogenase A attenuates pulmonary inflammation during acute lung injury. FASEB J. 2021 Apr; 35 (4): e21468. doi: 10.1096/fj.202002778R.Vohwinkel C.U., Coit E.J., Burns N., Elajaili H., Hernandez-Saavedra D., Yuan X. et al. Targeting alveolar-specific succinate dehydrogenase A attenuates pulmonary inflammation during acute lung injury. FASEB J. 2021 Apr; 35 (4): e21468. doi: 10.1096/fj.202002778R.Mills E.L., Pierce K.A., Jedrychowski M.P., Garrity R., Winther S., Vidoni S., Yoneshiro T., Spinelli J.B., Lu G.Z., Kazak L., Banks A.S., Haigis M.C., Kajimura S., Murphy M.P., Gygi S.P., Clish C.B., Chouchani E.T. Accumulation of succinate controls activation of adipose tissue thermogenesis. Nature. 2018 Aug; 560 (7716): 102–106. doi: 10.1038/s41586-018-0353-2.Mills E.L., Pierce K.A., Jedrychowski M.P., Garrity R., Winther S., Vidoni S., Yoneshiro T., Spinelli J.B., Lu G.Z., Kazak L., Banks A.S., Haigis M.C., Kajimura S., Murphy M.P., Gygi S.P., Clish C.B., Chouchani E.T. Accumulation of succinate controls activation of adipose tissue thermogenesis. Nature. 2018 Aug; 560 (7716): 102–106. doi: 10.1038/s41586-018-0353-2.Александрович Ю. С., Пшениснов К. В., Красносельский К. Ю. и др. Влияние растворов на основе субстратов цикла трикарбоновых кислот на показатели температуры у детей во время анестезии. Анестезиология и реаниматология. 2017; 62 (1): 28–32. doi: https://doi.org/10.18821/0201-7563-2017-62-1-29-32.Aleksandrovich Jyu. S., Pshenisnov K. V., Krasnosel'skij K. Jyu. i dr. Vliyanie rastvorov na osnove substratov tsikla trikarbonovykh kislot na pokazateli temperatury u detej vo vremya anestezii. Anesteziologiya i Reanimatologiya. 2017; 62 (1): 28– 32. doi: https://doi.org/10.18821/0201-7563-2017-62-1-29-32. (in Russian)Александрович Ю.С., Юрьев О.В., Пшениснов К.В., Красносельский К.Ю. Интраоперационаая коррекция нарушений температурного гомеостаза у детей. Экспериментальная и клиническая фармакология. 2012; 75 (5): 39–43.Aleksandrovich Jyu.S., Jyur'ev O.V., Pshenisnov K.V., Krasnosel'skij K.Jyu. Intraoperatsionaaya korrektsiya narushenij temperaturnogo gomeostaza u detej. Eksperimental'naya i Klinicheskaya Farmakologiya. 2012; 75 (5): 39–43. (in Russian)Красносельский К.Ю., Александрович Ю.С., Гордеев В.И., Лосев Н.А. О возможности управления интраоперационным термогенезом. Анестезиология и реаниматология. 2007; 3: 33–35.Krasnosel'skij K.Jyu., Aleksandrovich Jyu.S., Gordeev V.I., Losev N.A. O vozmozhnosti upravleniya intraoperatsionnym termogenezom. Anesteziologiya i Reanimatologiya. 2007; 3: 33–35. (in Russian)Ivnitsky J.J., Rejniuk V.L., Schäfer T.V., Malakhovsky V.N. Succinate and artificial maintenance of normal body temperature synergistically correct lethal disorders in thiopental coma rat. Toxicology. 2006 Jan 20; 218 (1): 22–29. doi: 10.1016/j.tox.2005.09.006.Ivnitsky J.J., Rejniuk V.L., Schäfer T.V., Malakhovsky V.N. Succinate and artificial maintenance of normal body temperature synergistically correct lethal disorders in thiopental coma rat. Toxicology. 2006 Jan 20; 218 (1): 22–29. doi: 10.1016/j.tox.2005.09.006.Choi I., Son H., Baek J.H. Tricarboxylic acid (TCA) cycle intermediates: regulators of immune responses. Life (Basel). 2021 Jan 19; 11 (1): 69. doi: 10.3390/life11010069.Choi I., Son H., Baek J.H. Tricarboxylic acid (TCA) cycle intermediates: regulators of immune responses. Life (Basel). 2021 Jan 19; 11 (1): 69. doi: 10.3390/life11010069.Harber K.J., de Goede K.E., Verberk S.G.S., Meinster E., de Vries H.E., van Weeghel M., de Winther M.P.J., Van den Bossche J. Succinate is an inflammation-induced immunoregulatory metabolite in macrophages. Metabolites. 2020; 10: 372. doi: 10.3390/metabo10090372.Harber K.J., de Goede K.E., Verberk S.G.S., Meinster E., de Vries H.E., van Weeghel M., de Winther M.P.J., Van den Bossche J. Succinate is an inflammation-induced immunoregulatory metabolite in macrophages. Metabolites. 2020; 10: 372. doi: 10.3390/metabo10090372.Mills E.L., Kelly B., Logan A., Costa A.S.H., Varma M., Bryant C.E., Tourlomousis P., Däbritz J.H.M., Gottlieb E., Latorre I. et al. Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages. Cell. 2016; 167: 457–470. e13. doi: 10.1016/j.cell.2016.08.064.Mills E.L., Kelly B., Logan A., Costa A.S.H., Varma M., Bryant C.E., Tourlomousis P., Däbritz J.H.M., Gottlieb E., Latorre I. et al. Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages. Cell. 2016; 167: 457–470. e13. doi: 10.1016/j.cell.2016.08.064.

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