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Success of Succinates and Prospects for Their Use in Critical Conditions

https://doi.org/10.37489/0235-2990-2024-69-7-8-80-91.

Abstract

To date, preparations containing succinic acid (succinate) are widely known to specialists working in intensive care. Several such preparations have gained wide acclaim among anesthesiologists and resuscitators, namely: Reamberin, infusion solution — a crystalloid preparation containing 1.5% meglumine sodium succinate; Remaxol, infusional solution – a complex infusional solution containing, in addition to succinic acid, nicotinamide, inosine, as well as the aliphatic α-amino acid methionine (which serves in the body as a donor of methyl groups in S-adenosyl-methionine during the biosynthesis of choline, adrenaline, etc., and is also a source of sulfur during the biosynthesis of cysteine); Cytoflavin, a solution for intravenous administration, containing a complex of two vital vitamins necessary to provide a pool of coenzymes — B2 in the form of a highly water-soluble form of riboflavin mononucleotide and PP in the form of nicotinic acid amide, succinic acid, and inosine (riboxin), as well as succinic acid itself. However, some skeptics have not been convinced yet, they oppose the use of these medications in the treatment of critical conditions. The purpose of this article is to expand our views on the natural essence of succinates, their biological role in the human body, highlighting the existing experience of their use in critical conditions, as well as the possibility of their use in the future.

About the Authors

S. V. Sviridov
Pirogov Russian National Research Medical University
Russian Federation

Sergey V. Sviridov — D. Sc. in Medicine, Professor, Head of the Department of Anesthesiology, Resuscitation, and Intensive Care named after Professor V. D. Malyshev, Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation

Moscow



A. V. Butrov
Peoples' Friendship University of Russia
Russian Federation

Andrey V. Butrov — D. Sc. in Medicine, Laureate of the USSR State Prize, Chairman of the Association of Anesthesiologists and Resuscitators of the Central Federal District, Professor of the Department of Anesthesiology and Resuscitation, Medical Institute of the Peoples' Friendship University of Russia

Moscow



V. V. Afanasyev
North-Western State Medical University named after I. I. Mechnikov of the Ministry of Health of the Russian Federation
Russian Federation

Vasily V. Afanasyev — D. Sc. in Medicine, Member of the WHO Toxicology Section (INTOX project), Laureate of the Merck International Fellowship in Clinical Pharmacology and Clinical Toxicology (University of Colorado, USA), member of the American Academy of Clinical Toxicology; Professor of the Department of Emergency Medical Care, North-Western State Medical University named after I. I. Mechnikov of the Ministry of Health of the Russian Federation, Chief Clinical Toxicologist of the Leningrad Region

St. Petersburg



Yu. P. Orlov
Omsk State Medical University of the Ministry of Health of the Russian Federation
Russian Federation

Yurii P. Orlov — D. Sc. in Medicine, Associate Professor, Professor of the Department of Anesthesiology and Resuscitation, Omsk State Medical University of the Ministry of Health of the Russian Federation

Omsk



A. Yu. Petrov
Saint Petersburg State University, «Medical Institute of Saint Petersburg State University»
Russian Federation

Andrey Yu. Petrov — Ph. D. in Pharmaceutical Sciences, Laureate of the Russian Federation Government Prize in Science and Technology, Saint Petersburg State University, «Medical Institute of Saint Petersburg State University»

Saint Petersburg



References

1. Chekman I. S., Syrovaya A. O., Makarov V. A., Makarov V. V., Lapshin V. V. Yantar', yantarnaya kislota, suktsinaty. Monografiya. Kiev; Khar'kov: Planeta-print, 2017; 107. (in Russian)

2. Buranova D. D. The value of Avicenna's heritage in development of modern integrative medicine in Uzbekistan. Integr Med Res. 2015 Dec; 4 (4): 220–224. doi: 10.1016/j.imr.2015.06.002.

3. Trifonov G.B., Trifonova S.D., Petrov S.G. Rossiya-naslednitsa prusskikh znanij o yantare. Istoriya. Nauka. Praktika. Budushchee. Izdatel'stvo LAP LAMBERT Academic Publishing. 2014. (in Russian)

4. Maevskij E.I., Grishina E.V., Rozenfel'd A.S. i dr. Anaerobnoe obrazovanie suktsinata i oblegchenie ego okisleniya — vozmozhnye mekhanizmy adaptatsii kletki k kislorodnomu golodanijyu. Biomed zhurn. 2000; 1: 32–36. (in Russian)

5. Zarzhetskij Jyu.V., Mutuskina E.A., Trubina I.E. i dr. Vliyanie suktsinata natriya na funktsional'nye, biokhimicheskie i morfologicheskie pokazateli vosstanovleniya TsNS u krys posle 10-minutnoj ostanovki krovoobrashcheniya. Anesteziol i reanimatol. 1994; 5: 96–103. (in Russian)

6. Skulachev V.P. Briton Chans. Biokhimiya. 2011; 76: 3: 459–460. (in Russian)

7. Chance B., Williams G. R. Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization. J Biol Chem. 1955; 217 (1): 383–393.

8. Chance B., Williams, G.R. The respiratory chain and oxidative phosphorylation. Adv Enzymol Relat Subj Biochem. 1956;17: 65–134.

9. Anisimov V.N., Kondrashova M.N. Vliyanie yantarnoj kisloty na chastotu spontannykh opukholej i prodolzhitel'nost' zhizni myshej SZN/Sn, Dokl. AN SSSR. 1979; 248 (5): 1242. (in Russian)

10. Terapevticheskoe dejstvie yantarnoj kisloty. M. N. Kondrashova (ed.), Pushchino, 1976.

11. Kondrashova M.N., Gogvadze V.G., Medvedev B.I., Babsky A.M. Succinic acid oxidation as the only energy support of intensive Ca2+ uptake by mitochondria. Biochem Biophys Res Commun. 1982 Nov 30; 109 (2): 376–381. doi: 10.1016/0006-291x(82)91731-4.

12. He W., Miao F.J., Lin D.C., Schwandner R.T., Wang Z., Gao J. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature. 2004; 429: 188–193.

13. Prabhakar N.R. 2019 Nobel Prize in Physiology or Medicine. Physiology (Bethesda). 2020 Mar 1; 35 (2): 81–83. doi: 10.1152/physiol.00001.2020. PMID: 32024429.

14. Briston T., Roberts M., Lewis S., Powney B., M. Staddon J., Szabadkai G., Duchen M.R. Mitochondrial permeability transition pore: sensitivity to opening and mechanistic dependence on substrate availability. Sci Rep. 2017 Sep 5; 7 (1):10492. doi: 10.1038/s41598-017-10673-8.

15. Kohler A., Barrientos A., Fontanesi F., Ott M. The functional significance of mitochondrial respiratory chain supercomplexes. EMBO Rep. 2023 Nov 6; 24 (11): e57092. doi: 10.15252/embr.202357092.

16. Hawkins B.J., Levin M.D., Doonan P.J., Petrenko N.B., Davis C.W., Patel V.V., Madesh M. Mitochondrial complex II prevents hypoxic but not calcium- and proapoptotic Bcl-2 protein-induced mitochondrial membrane potential loss. J Biol Chem. 2010 Aug 20; 285 (34): 26494–26505. doi: 10.1074/jbc.M110.143164.

17. Lenaz G., Genova M.L. Kinetics of integrated electron transfer in the mitochondrial respiratory chain: random collisions vs. solid state electron channeling. Am J Physiol Cell Physiol. 2007 Apr; 292 (4): C1221-39. doi: 10.1152/ajpcell.00263.2006.

18. Andrienko T.N., Pasdois P., Pereira G.C., Ovens M.J., Halestrap A.P. The role of succinate and ROS in reperfusion injury — A critical appraisal. J Mol Cell Cardiol. 2017 Sep; 110: 1–14. doi: 10.1016/j.yjmcc.2017.06.016.

19. Afanas'ev V.V. Tsitoflavin v intensivnoj terapii: Posobie dlya vrachej. SPb.: 2005;-36: 9–30. (in Russian)

20. 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.

21. Krebs H.A., Eggleston L.V., D’Alessandro A. The effect of succinate and amytal on the reduction of acetoacetate in animal tissues. Biochem J. 1961; 79: 537–549.

22. Chance B., Hollunger G. The interaction of energy and electron transfer reactions in mitochondria: 1. General properties and nature of the products of succinate-linked reduction of pyridine nucleotide. J Biol Chem. 1961; 236 (5): 1534–1543.

23. Dienel G.A., Cruz N.F. Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism. J Neurochem. 2016 Jul; 138 (1): 14–52. doi: 10.1111/jnc.13630.

24. Mejes P. Okislitel'noe fosforilirovanie i transportnye sistemy mitokhondrij. V: Marri R., Grenner D., Mejes P., Roduell V. Biokhimiya cheloveka. Mir, M.: 2009; 1: 127–139. (in Russian)

25. Luk'yanova L.D. Signal'nye mekhanizmy gipoksii. M.: RAN, 2019; 215. (in Russian)

26. Tolkach A.B., Dolgikh V.T. Vliyanie reamberina na kislorodnyj balans, okislitel'nyj stress i legochnujyu disfunktsijyu u patsientov c abdominal'nym sepsisom. Bjyulleten' sibirskoj meditsiny. 2012; 11(3): 69–75. doi: https://doi.org/10.20538/1682-0363-2012-3-69-75. (in Russian)

27. Orlov Jyu.P., Lukach V.N., Glushchenko A.V. Reamberin v programme intensivnoj terapii u patsientov s rasprostranennym peritonitom. Novosti khirurgii. 2013; 21 (5): 58–64. (in Russian)

28. Livanov G.A., Batotsyrenov B.V., Vasil'ev S.A., Andrianov A.Jyu., Baranov D.V., Nezhentseva I.V. Okislitel'nyj distress i ego korrektsiya reamberinom u bol'nykh s ostrym otravleniem smes'jyu psikhotropnykh veshchestv. Obshchaya reanimatologiya. 2013; 9 (5): 18. doi: https://doi.org/10.15360/1813-9779-2013-5-18. (in Russian)

29. Guillon A., Brea-Diakite D., Cezard A., Wacquiez A., Baranek T., Bourgeais J., Picou F., Vasseur V., Meyer L., Chevalier C., Auvet A., Carballido J.M., Nadal Desbarats L., Dingli F., Turtoi A., Le Gouellec A., Fauvelle F., Donchet A., Crépin T., Hiemstra P.S., Paget C., Loew D., Herault O., Naffakh N., Le Goffic R., Si-Tahar M. 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.

30. Vohwinkel C.U., Coit E.J., Burns N., Elajaili H., Hernandez-Saavedra D., Yuan X., Eckle T., Nozik E., Tuder R.M., Eltzschig H.K. 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. PMID: 33687752.

31. Antonioli L., Blandizzi C., Pacher P., Haskó G. Immunity, inflammation and cancer: a leading role for adenosine. Nat Rev Cancer. 2013 Dec; 13 (12): 842–57. doi: 10.1038/nrc3613.

32. Eltzschig H.K., Sitkovsky M.V., Robson S.C. Purinergic signaling during inflammation. N Engl J Med. 2012 Dec 13; 367 (24): 2322–2333. doi: 10.1056/NEJMra1205750.

33. Serhan C.N., Chiang N., Dalli J., Levy B.D. Lipid mediators in the resolution of inflammation. Cold Spring Harb Perspect Biol. 2014 Oct 30; 7 (2): a016311. doi: 10.1101/cshperspect.a016311.

34. Moyon A., Garrigue P., Balasse L., Fernandez S., Brige P., Bouhlel A., Hache G., Dignat-George F., Taïeb D., Guillet B. Succinate Injection rescues vasculature and improves functional recovery following acute peripheral ischemia in rodents: a multimodal imaging study. Cells. 2021 Apr 2; 10 (4): 795. doi: 10.3390/cells10040795.

35. Sapieha P., Sirinyan M., Hamel D., Zaniolo K., Joyal J.-S., Cho J.-H., Honoré J.-C., Kermorvant-Duchemin E., Varma D.R., Tremblay S. et al. The succinate receptor GPR91 in neurons has a major role in retinal angiogenesis. Nat Med. 2008; 14: 1067–1076. doi: 10.1038/nm.1873.

36. Wang T., Xu Y.Q., Yuan Y.X., Xu P.W., Zhang C., Li F., Wang L.N., Yin C., Zhang L., Cai X.C., Zhu C.J., Xu J.R., Liang B.Q., Schaul S., Xie P.P., Yue D., Liao Z.R., Yu L.L., Luo L., Zhou G., Yang J.P., He Z.H., Du M., Zhou Y.P., Deng B.C., Wang S.B., Gao P., Zhu X.T., Xi Q.Y., Zhang Y.L., Shu G., Jiang Q.Y. Succinate induces skeletal muscle fiber remodeling via SUCNR1 signaling. EMBO Rep. 2020 May 6; 21 (5): e50461. doi: 10.15252/embr.202050461.

37. Germanova E., Khmil N., Pavlik L., Mikheeva I., Mironova G., Lukyanova L. The role of mitochondrial enzymes, succinate-coupled signaling pathways and mitochondrial ultrastructure in the formation of urgent adaptation to acute hypoxia in the myocardium. Int J Mol Sci. 2022 Nov 17;23(22):14248. doi: 10.3390/ijms232214248.

38. 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.

39. Xu G., Yuan Y., Luo P., Yang J., Zhou J., Zhu C., Jiang Q., Shu G. Acute succinate administration increases oxidative phosphorylation and skeletal muscle explosive strength via SUCNR1. Front Vet Sci. 2022 Jan 14;8:808863. doi: 10.3389/fvets.2021.808863.

40. Chapela S., Muscogiuri G., Barrea L., Frias-Toral E., Burgos H., Ricart M., Muryan A., Schiel A., Alonso M., Alberto Stella C. Parenteral succinate reduces levels of reactive oxygen species without changing serum caspase-3 levels in septic rats. Anaesthesiol Intensive Ther. 2022; 54 (5): 357–364. doi: 10.5114/ait.2022.122549.

41. 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.

42. 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.

43. Protti A., Carré J., Frost M. T. et al. Succinate recovers mitochondrial oxygen consumption in septic rat skeletal muscle. Critical Care Medicine. 2007; 35 (9): 2150–2155.

44. Piel S., Chamkha I., Dehlin A.K., Ehinger J.K., Sjövall F., Elmér E., Hansson M.J. Cell-permeable succinate prodrugs rescue mitochondrial respiration in cellular models of acute acetaminophen overdose. PLoS One. 2020 Apr 6; 15 (4): e0231173. doi: 10.1371/journal.pone.0231173.

45. Mazina N. K., Mazin P. V. Metaanalytic approach to evaluate clinical effectiveness of infusion succinnate-containing Remaxol in liver pathologies of diverse genesis. Antibiot Khimioter = Antibiotics and Chemotherapy. 2015, 60; 11–12: 43–49. (in Russian)

46. Bețiu A.M., Chamkha I., Gustafsson E., Meijer E., Avram V.F., Åsander Frostner E., Ehinger J.K., Petrescu L., Muntean D.M., Elmér E. Cell-permeable succinate rescues mitochondrial respiration in cellular models of amiodarone toxicity. Int J Mol Sci. 2021 Oct 29;22(21):11786. doi: 10.3390/ijms222111786.

47. 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.

48. Ferro A., Carbone E., Zhang J., Marzouk E., Villegas M., Siegel A., Nguyen D., Possidente T., Hartman J., Polley K., Ingram M.A., Berry G., Reynolds T.H., Possidente B., Frederick K., Ives S., Lagalwar S. Short-term succinic acid treatment mitigates cerebellar mitochondrial OXPHOS dysfunction, neurodegeneration and ataxia in a Purkinje-specific spinocerebellar ataxia type 1 (SCA1) mouse model. PLoS One. 2017 Dec 6; 12 (12): e0188425. doi: 10.1371/journal.pone.0188425.

49. Ferro A. et al. (2017). Treating SCA1 mice with water‐soluble compounds to non‐specifically boost mitochondrial function. Journal of Visualized Experiments, (119): 53758.

50. Ives S.J., Zaleski K.S., Slocum C., Escudero D., Sheridan C., Legesse S., Vidal K., Lagalwar S., Reynolds T.H. The effect of succinic acid on the metabolic profile in high-fat diet-induced obesity and insulin resistance. Physiol Rep. 2020 Nov; 8 (21): e14630. doi: 10.14814/phy2.14630.

51. Bogolepova A.N. Vozmozhnosti terapii nevrologicheskikh oslozhnenij sakharnogo diabeta Nervnye Bolezni. 2023; 1: 66–70. doi: https://doi.org/10.24412/2226- 0757-2023-12848. (in Russian)

52. Shakh B.N., Lapshin V.N., Kyrnyshev A.G., Smirnov D.B., Kravchenko-Berezhnaya N.R. Metabolicheskie effekty substratnogo antigipoksanta na osnove yantarnoj kisloty. Obshchaya Reanimatologiya. 2014; 10(1): 33–42. doi: https://doi.org/10.15360/1813-9779-2014-1-33-42. (in Russian)

53. Klimov A.G., Birjyukov A.N., Tarasenko M.Jyu., Gritsaj A.N., Strukov E.Jyu. Ispol'zovanie reamberina pri provedenii protivoshokovoj terapii u tyazhelo obozhzhennykh. Khirurgiya. Zhurnal im. N.I. Pirogova. 2020; 2: 95–99. doi: https://doi.org/10.17116/hirurgia202002195. (in Russian)

54. Pavelkina V.F., Erovichenkov A.A., Pak S.G. Sovershenstvovanie patogeneticheskoj terapii pri zabolevaniyakh bakterial'noj etiologii. Zhurnal Infektologii. 2012; 4 (3): 67–75. doi: https://doi.org/10.24411/0235-2990-2018-00021. (in Russian)

55. Petuhov V.A., Semenov Zh.S. Peritonit i endotelial'naya disfunkciya. V.S.Saveleva (ed.). «Maks Press», Moscow: 2011; 156. (in Russian)

56. Simutis I.S, Boyarinov G.A., Jyur'ev M.Jyu., Petrovskij D.S., KovalenkoA.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)

57. 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)

58. Livanov G.A., Lodyagin A.N., Batotsyrenov B.V., Loladze A.T., Glushkov S.I., Kovalenko A.L. Ispol'zovanie reamberina v komplekse intensivnoj terapii ostrykh otravlenij. Klinicheskaya Meditsina. 2016; 94 (5): 339–346. doi: https://doi.org/10.18821/0023-2149-2016-94-5-339-346. (in Russian)]

59. Lkhagvadorzh Ch., Sodnom Jyu. Vkljyuchenie Reamberina v skhemu infuzionnoj terapii patsientov s alkogol'noj intoksikatsiej. Eksperimental'naya i Klinicheskaya Farmakologiya. 2020; 6: 14–18. doi: https://doi.org/10.30906/0869-2092-2020-83-6-14-18. (in Russian)

60. 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)]

61. Kljyujko D.A., Korik V.E, Zhidkov S.A. Primenenie tsitoflavina v kompleksnom lechenii ostrogo pankreatita. Novosti Khirurgii. 2012; 20 (3): 22–27. (in Russian)

62. Salikhova K.Sh., Rustamova M.Sh., Salimov Sh.T., Abdusamatov B.Z. Vliyanie tsitoflavina na effektivnost' intensivnoj terapii novorozhdennykh s nekrotizirujyushchim enterokolitom. Voprosy Prakticheskoj Pediatrii. 2021; 16 (6): 63–67. doi: https://doi.org/10.20953/1817-7646-2021-6-63-67. (in Russian)


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For citations:


Sviridov S.V., Butrov A.V., Afanasyev V.V., Orlov Yu.P., Petrov A.Yu. Success of Succinates and Prospects for Their Use in Critical Conditions. Antibiot Khimioter = Antibiotics and Chemotherapy. 2024;69(7-8):80-91. (In Russ.) https://doi.org/10.37489/0235-2990-2024-69-7-8-80-91.

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