CORRECTION OF NEURO-IMMUNE DISORDERS ON THE MODEL OF POST-VIRAL CHRONIC FATIGUE SYNDROME WITH THE DRUG SODIUM DEOXYNUCLEAT (DERINAT)



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Abstract

Introduction. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is defined as a chronic illness characterized by severe fatigue, sleep disturbances, memory and concentration issues, and malaise following physical exertion, often manifesting after a viral infection.

The goal was to investigate the possibility of correcting manifestations of fatigue and neuroinflammation using a nucleotide-based drug (sodium deoxyribonucleate) in a model of chronic fatigue syndrome according to Katafuchi.

Materials and Methods. The study was conducted on 50 male Wistar rats. The disease was modeled through a single intraperitoneal administration of Poly IC at a dose of 3 mg/kg body weight. Half of the subjects received sodium deoxyribonucleate on the first day after syndrome induction. On days 7 and 10 of the experiment, we recorded motor activity, emotional status, and physical fatigue levels. After sample collection, we determined the concentration of lactic acid in plasma, the expression levels of genes (IL-1β, IL10, INFα, 5HTT, TLR3) in the hypothalamus, and the activity of splenic lymphocytes (cytotoxic and proliferative) as markers of immune system status.

Results. It was shown that a single administration of sodium deoxyribonucleate had a positive effect on metabolic processes (lactate levels after exercise), improved exploratory activity, and reduced the level of anxiety-like behavior, reduced anxiety-like behavior, normalized the depressed cytotoxic and proliferative activity of splenic lymphocytes, and restored excessive expression of all studied genes in the hypothalamus to normal levels, which was not observed in untreated rats.

Conclusion. The administration of sodium deoxyribonucleate to animals did not eliminate the characteristic muscle weakness but accelerated the normalization of physical activity and emotional status, reducing anxiety manifestations by day 7 of the experiment, rather than day 10 as seen in the untreated rat group.

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About the authors

Natalia B. Serebryanaya

Institute of Experimental Medicine

Author for correspondence.
Email: nbvma@mail.ru
ORCID iD: 0000-0002-2418-9368
SPIN-code: 2240-1277
Scopus Author ID: 6701636993
ResearcherId: G-1663-2015

MD, Dr. Sci. (Medicine), Professor, Head of the General Immunology Lab

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Tatiana A. Filatenkova

Institute of Experimental Medicine

Email: lero269@gmail.com
ORCID iD: 0000-0002-6911-7456
SPIN-code: 4198-3636

Researcher of the Laboratory of Anticancer Peptide Drugs of the Department of General Pathology and Pathophysiology

Russian Federation, Saint Petersburg

Sergey N. Shanin

Institute of Experimental Medicine

Email: shanins@yandex.ru
ORCID iD: 0000-0001-8829-6552
SPIN-code: 6915-9098

MD, Cand. Sci. (Medicine), Senior Researcher, Laboratory of Immunopathophysiology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Elena E. Fomicheva

Institute of Experimental Medicine

Email: eefomicheva@rambler.ru
ORCID iD: 0000-0001-9271-9757
SPIN-code: 2655-3338

Cand. Sci. (Biology), Senior Researcher, Laboratory of Immunopathophysiology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

References

  1. Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Board on the Health of Select Populations; Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington (DC): National Academies Press (US); 2015 Feb 10. PMID: 25695122.
  2. Estevez-Lopez F., Mudie K., Wang-Steverding X., Bakken I.J., Ivanovs A., et al. Systematic review of the epidemiological burden of myalgic encephalomyelitis/chronic fatigue syndrome across Europe: current evidence and EUROMENE research recommendations for epidemiology. J. Clin. Med. 2020;9(5):1557. doi: 10.3390/jcm9051557.
  3. Vahratian A, Lin JS, Bertolli J, Unger ER. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Adults: United States, 2021-2022. NCHS Data Brief. 2023 Dec;(488):1-8. PMID: 38085820.
  4. Cortes Rivera M, Mastronardi C, Silva-Aldana CT, Arcos-Burgos M, Lidbury BA. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Comprehensive Review. Diagnostics (Basel). 2019 Aug 7;9(3):91. doi: 10.3390/diagnostics9030091
  5. Nakatomi Y, Mizuno K, Ishii A, Wada Y, Tanaka M, Tazawa S, Onoe K, Fukuda S, Kawabe J, Takahashi K, Kataoka Y, Shiomi S, Yamaguti K, Inaba M, Kuratsune H, Watanabe Y. Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. J Nucl Med. doi: 10.2967/jnumed.113.131045.
  6. Rhoades R, Solomon S, Johnson C, Teng S. Impact of SARS-CoV-2 on Host Factors Involved in Mental Disorders. Front Microbiol. 2022 Apr 4;13:845559. doi: 10.3389/fmicb.2022.845559
  7. Katafuchi Т., Kondo Т., Yasaka Т., Kubo К., Take S. Prolonged effects of polyriboinosinic: polyribocytidylic acid on spontaneous running wheel activity and brain interferon alfa mRNA in rats: a model for immunologically induced fatigue // Neuroscience. - 2003. - Vol.120. - P.837-845
  8. Wörnle M, Sauter M, Kastenmüller K, Ribeiro A, Mussack T, Ladurner R, Sitter T. Role of viral receptors TLR3, RIG-I and MDA5 in mesothelial tissue-type plasminogen activator and plasminogen activator inhibitor-1 synthesis. Thromb Haemost. 2009 Jun;101(6):1128-37. doi: 10.1160/th08-11-0744
  9. Filatenkova T.A., Shanin S.N., Fomicheva E.E., Korneva E.A., Serebryanaya N.B. Experimental model of CFS: cognitive, physical and metabolic indicators of pathology development // Medical Academic Journal. - 2019. - Vol.19, No.1S. https://doi.org/10.17816/MAJ191S174-76
  10. Fomicheva E.E., Filatenkova T.A. Dysfunction of the HPA axis in an experimental model of chronic fatigue syndrome // Psychopharmacology and biological narcology. 2008. No.1-2-2. URL: https://cyberleninka.ru/article/n/narushenie-funktsiy-ggaks-v-eksperimentalnoy-modeli-sindroma-hronicheskoy-ustalosti
  11. Rybakina E.G., Shanin S.N., Fomicheva E.E., Kozinets I.A., Filatenkova T.A., Dmitrienko E.V. Disturbances in the interaction of the immune and neuroendocrine systems during stress, chronic fatigue syndrome and methods for their correction // Medical Academic Journal. - 2010. - V. 10. - No. 4. - P. 161-174. doi: 10.17816/MAJ104161-174
  12. Fomicheva E.E., Shanin S.N., Filatenkova T.A., Rybakina E.G., Korneva E.A. Serotonergic system of the brain in the development of neuroimmune interaction disorders during chronic fatigue modeling // Bulletin of St. Petersburg University. Medicine. 2015. No. 3. URL: https://cyberleninka.ru/article/n/serotoninergicheskaya-sistema-mozga-v-razvitii-narusheniy-neyroimmunnogo-vzaimodeystviya-pri-modelirovanii-hronicheskoy-ustalosti
  13. Kaplina E.N., Weinberg Yu.P. Derinat - a natural immunomodulator for children and adults. 3rd ed., corrected. and add. M.: Nauchnaya Kniga, 2007. 240 p. [Kaplina EN, Vaynberg YuP. Derinat - a natural immunomodulator for children and adults. Moscow: Nauchnaya Kniga Publ., 2007. 240 p. (in Russian)]
  14. Rybakina E. G., Shanin S. N., Fomicheva E. E., Kozinets I. A., Korneva E. A. Activity of the body's protective functions under stress and their correction with the drug Derinat // Medical Immunology. 2008. No. 4-5. URL: https://cyberleninka.ru/article/n/aktivnost-zaschitnyh-funktsiy-organizma-pri-stresse-i-ih-korrektsiya-preparatom-derinat.
  15. Fais A, Cacace E, Corda M, Era B, Peri M, Utzeri S, Ruggiero V. Purine metabolites in fibromyalgia syndrome. Clin Biochem. 2013 Jan;46(1-2):37-9. doi: 10.1016/j.clinbiochem.2012.09.009.
  16. Guieu R, Guedj E, Giorgi R, Dousset A, Tuzzolino V, By Y, Leveque JM, Peragut JC, Régis J, Ruf J, Fenouillet E, Roussel P. High cell surface CD26-associated activities and low plasma adenosine concentration in fibromyalgia. Ann Rheum Dis. 2012 Aug;71(8):1427-8. doi: 10.1136/annrheumdis-2011-201174.
  17. Bazzichi L, Giannaccini G, Betti L, Fabbrini L, Schmid L, Palego L, Giacomelli C, Rossi A, Giusti L, De Feo F, Giuliano T, Mascia G, Bombardieri S, Lucacchini A. ATP, calcium and magnesium levels in platelets of patients with primary fibromyalgia. Clin Biochem. 2008 Sep;41(13):1084-90. doi: 10.1016/j.clinbiochem.2008.06.012.
  18. Castro-Marrero J, Cordero MD, Sáez-Francas N, Jimenez-Gutierrez C, Aguilar-Montilla FJ, Aliste L, Alegre-Martin J. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia? Antioxid Redox Signal. 2013 Nov 20;19(15):1855-60. doi: 10.1089/ars.2013.5346. PMID: 23600892.
  19. Gerdle B, Ghafouri B, Lund E, Bengtsson A, Lundberg P, Ettinger-Veenstra HV, Leinhard OD, Forsgren MF. Evidence of Mitochondrial Dysfunction in Fibromyalgia: Deviating Muscle Energy Metabolism Detected Using Microdialysis and Magnetic Resonance. J Clin Med. 2020 Oct 31;9(11):3527. doi: 10.3390/jcm911352
  20. Mantle D, Hargreaves IP, Domingo JC, Castro-Marrero J. Mitochondrial dysfunction and coenzyme Q10 supplementation in post-viral fatigue syndrome: an overview. Int J Mol Sci. 2024;25(1):574. 10.3390/ijms25010574. 10.3390/ijms25010574.
  21. Molnar T, Lehoczki A, Fekete M, Varnai R, Zavori L, Erdo-Bonyar S, Simon D, Berki T, Csecsei P, Ezer E. Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches. Geroscience. 2024 Oct;46(5):5267-5286. doi: 10.1007/s11357-024-01165-5.
  22. Nascimento FP, Macedo-Júnior SJ, Lapa-Costa FR, Cezar-Dos-Santos F, Santos ARS. Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor? Front Neurosci. 2021; 15:703783. doi: 10.3389/fnins.2021.703783.
  23. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. London: National Institute for Health and Care Excellence (NICE); 2021 Oct 29. PMID: 35438859.
  24. Tomas C, Lodge TA, Potter M, Elson JL, Newton JL, Morten KJ. Assessing cellular energy dysfunction in CFS/ME using a commercially available laboratory test. Sci Rep. 2019; 9(1):11464. doi: 10.1038/s41598-019-47966-z.
  25. Sweetman E, Noble A, Edgar C, Mackay A, Helliwell A, Vallings R, Ryan M, Tate W. Current Research Provides Insight into the Biological Basis and Diagnostic Potential for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Diagnostics (Basel). 2019 Jul 10;9(3):73. doi: 10.3390/diagnostics9030073.
  26. Fluge Ø, Mella O, Bruland O, Risa K, Dyrstad SE, Alme K, Rekeland IG, Sapkota D, Røsland GV, Fosså A, Ktoridou-Valen I, Lunde S, Sørland K, Lien K, Herder I, Thürmer H, Gotaas ME, Baranowska KA, Bohnen LM, Schäfer C, McCann A, Sommerfelt K, Helgeland L, Ueland PM, Dahl O, Tronstad KJ. Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome. JCI Insight. 2016 Dec 22;1(21):e89376. doi: 10.1172/jci.insight.89376.
  27. Dedov I.I., Troshina E.A., Mazurina N.V., Galieva M., Logvinova O.V. The role of neurotransmitters in the regulation of energy homeostasis and the possibility of drug correction of its disorders in obesity. Obesity and Metabolism. 2016;13(1):9-15. https://doi.org/10.14341/omet201619-15
  28. Gozal EA, O'Neill BE, Sawchuk MA, Zhu H, Halder M, Chou CC, Hochman S. Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord. Front Neural Circuits. 2014 Nov 7; 8:134. doi: 10.3389/fncir.2014.00134. Gozal EA, O'Neill BE, Sawchuk MA, Zhu H, Halder M, Chou CC, Hochman S. Anatomical and functional evidence for trace amines as unique modulators of locomotor function in the mammalian spinal cord. Front Neural Circuits. 2014 Nov 7; 8:134. doi: 10.3389/fncir.2014.00134.
  29. Maes M, Ringel K, Kubera M, Anderson G, Morris G, Galecki P, Geffard M. In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation. J Affect Disord. 2013 Sep 5;150(2):223-30. doi: 10.1016/j.jad.2013.03.029
  30. Lee JS, Kang JY, Park SY, Hwang SJ, Bae SJ, Son CG. Central 5-HTergic hyperactivity induces myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-like pathophysiology. J Transl Med. 2024 Jan 8;22(1):34. doi: 10.1186/s12967-023-04808-x.
  31. Nesterova IV, Balmasova IP, Kozlov VA, Malova ES, Se-piashvili RI. Chronic fatigue syndrome and immune dysfunction in patients with recurrent viral infections: Clinical im-munologic characteristic and features of serotonin regulation. Cytokines and Inflammation. 2006; 5(2): 3-14. eLIBRARY ID: 17015724, EDN: OIJFXF
  32. Song JH, Won SK, Eom GH, Lee DS, Park BJ, Lee JS, Son CG, Park JY. Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model. Int J Mol Sci. 2021 Sep 22;22(19):10199. doi: 10.3390/ijms221910199.
  33. Haleem DJ, Mahmood K. Brain serotonin in high-fat diet-induced weight gain, anxiety and spatial memory in rats. Nutr Neurosci. 2021 Mar;24(3):226-235. doi: 10.1080/1028415X.2019.1619983.
  34. Ifuku M, Hossain SM, Noda M, Katafuchi T. Induction of interleukin-1β by activated microglia is a prerequisite for immunologically induced fatigue. Eur J Neurosci. 2014 Oct;40(8):3253-63. doi: 10.1111/ejn.12668
  35. Katafuchi T, Kondo T, Take S, Yoshimura M. Enhanced expression of brain interferon-alpha and serotonin transporter in immunologically induced fatigue in rats. Eur J Neurosci. 2005 Dec;22(11):2817-26. doi: 10.1111/j.1460-9568.2005.04478.x.
  36. Le Naour J, Galluzzi L, Zitvogel L, Kroemer G, Vacchelli E. Trial watch: TLR3 agonists in cancer therapy. Oncoimmunology. 2020 Jun 2;9(1):1771143. doi: 10.1080/2162402X.2020.1771143
  37. Noda M, Ifuku M, Hossain MS, Katafuchi T. Glial Activation and Expression of the Serotonin Transporter in Chronic Fatigue Syndrome. Front Psychiatry. 2018; 9:589. doi: 10.3389/fpsyt.2018.00589
  38. Fomicheva E.E., Shanin S.N., Filatenkova T.A., Rybakina E.G. Stress-induced changes in the functional activity of the neuroendocrine system: modulating effect of the drug Derinat // Russian Physiological Journal named after I.M. Sechenov. - 2009. Vol. 95, No. 3. P. 290-296. eLIBRARY ID: 17015724, EDN: OIJFXF
  39. Rybakina E.G., Shanin S.N., Fomicheva E.E., et.al. Correction of stress-induced dysfunctions of the immune and neuroendocrine systems by peptide and nucleotide preparations // Advances in Neuroimmune Biology. – 2012. - Vol.3.-P. 353-36041. http://content.iospress.com/articles/advances-in-neuroimmune-biology/nib012902 [
  40. Rybakina E.G., Shanin S.N., Fomicheva E.E., Kozinets I.A., Korneva E.A. Activity of the body's protective functions under stress and their correction by the drug Derinat // Medical Immunology. - 2008. Vol.10, No.4-5. P. 431-438. https://doi.org/10.15789/1563-0625-2008-4-5-431-438
  41. Rusinova T. V., Chudilova G. A., Kolesnikova N. V. Comparative assessment of immunotropic effects in vitro of Derinat and synthetic TLR9 agonist on the receptor function of neutrophilic granulocytes and monocytes in normal conditions and during infectious processes // Kuban Scientific Medical Bulletin. 2016. No. 5. URL: https://cyberleninka.ru/article/n/sravnitelnaya-otsenka-immunotropnyh-effektov-in-vitro-derinata-i-sinteticheskogo-agonista-tlr9-na-retseptornuyu-funktsiyu-neytrofilnyh
  42. Kostyuk S.V., Malinovskaya E.M., Ermakov A.V., Smirnova T.D., Kameneva L.V., Chvartatskaya O.V., Loseva P.A., Ershova E.S., Lyubchenko L.N., Veiko N.N. Fragments of extracellular DNA enhance transcriptional activity of the human mesenchymal stem cell genome, activate the TLR-dependent signaling pathway and inhibit apoptosis. Biomedical Chemistry. 2012; 58 (6): 673-683. doi: 10.18097/pbmc20125806673
  43. Liu J, Rybakina E, Korneva E, Noda M. Effects of Derinat on ischemia-reperfusion-induced pressure ulcer mouse model. J.Pharm.Sci., 2018; 138(2):123-130. https://doi.org/10.1016/j.jphs.2018.08.013
  44. Nicholls, D. G.; Ferguson, S.J. Bioenergetics, 4th ed.; Academic Press: London, UK, 2013; 419p. doi: 10.1016/C2010-0-64902-9 : Paperback ISBN: 9780123884251, eBook ISBN: 9780123884312
  45. Dmitrienko E.V., Akimoto N., Naov S., Noda M., Rybakina E.G., Korneva E.A. The immune system of the brain and traumatic brain injury: an attempt at correction // Medical Academic Journal. - 2013. - V. 13. - No. 4. - P. 7-18. doi: 10.17816/MAJ1347-18

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