Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

(English title: Physiological Journal)

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2026; 72(2): 20-28

EFFECT OF QUERCETIN ON THE SYSTEMIC INFLAMMATORY RESPONSE AND METABOLIC ALTERATIONS IN REPETITIVE MILD TRAUMATIC BRAIN INJURY UNDER CHRONIC ALCOHOL INTOXICATION

I.M. Adamovych, H.V. Kostenko, O.Ye. Akimov, V.O. Kostenko

  1. Poltava State Medical University, Ukraine
DOI: https://doi.org/10.15407/fz72.02.020


Abstract

Repetitive mild traumatic brain injury (TBI) under chronic alcohol intoxication (CAI) represents a prevalent comorbid condition associated with neuroinflammation, metabolic disturbances, and an increased risk of chronic traumatic en- cephalopathy. The search for pharmacological agents capable of simultaneously mitigating neural tissue damage and cor- recting systemic metabolic dysregulation is of considerable scientific and clinical relevance. This study investigated the effects of quercetin on biomarkers of neural tissue injury, systemic inflammatory response parameters, and carbohydrate and lipid metabolism in rats subjected to repetitive mild TBI under CAI. The experiment was performed on Wistar rats di- vided into three groups: Group 1 (Control I) – intact animals; Group 2 – rats exposed to TBI combined with CAI (Control II); Group 3 – rats receiving an intraperitoneal water-soluble form of quercetin (Corvitin) at 100 mg/kg for 14 days follow- ing TBI with CAI. TBI was induced using a free-weight drop method (five sessions at 48-hour intervals), while CAI was modeled by administering 40% ethanol at 12 ml/kg for 14 days. Serum concentrations of neuron-specific enolase (NSE), calcium-binding protein S100B, tumor necrosis factor-alpha (TNF-α), interleukins (IL)-6 and IL-10, glucose, insulin, and lipid profile parameters were measured, and the HOMA-IR index was calculated. TBI combined with CAI resulted in marked neuroinflammation and systemic inflammatory re- sponse, as evidenced by significant elevations in neural tissue injury markers, increased serum levels of pro-inflammatory cytokines TNF-α and IL-6, and the development of insulin resistance and dyslipidemia. Administering quercetin led to significant reductions in serum NSE (61.9%), S100B (56.3%), TNF-α (40.8%), and IL-6 (42.0%), as well as a 187.5% in- crease in IL-10. Furthermore, compared with Group 2 values, the bioflavonoid reduced glucose by 30.5%, insulin by 68.7%, very low-density lipoproteins (VLDL) by 42.3%, triglycerides by 41.9%, and HOMA-IR by 78.4%. These findings indicate that quercetin exerts pronounced neuroprotective and anti- inflammatory effects under conditions of TBI combined with CAI, effectively lowering serum biomarkers of neural tissue injury and pro-inflammatory cytokines, while enhancing the anti-inflammatory cytokine IL-10. Moreover, quercetin effi- ciently restores metabolic homeostasis by normalising glyce- mia, improving insulin sensitivity, and reducing dyslipidemia.

Keywords: repetitive mild traumatic brain injury, neural tissue injury biomarkers, inflammation, cytokines, insulin, insulin resistance, quercetin, rats.

Full text: (PDF, in Ukrainian)

References

  1. Karaboue MAA, Ministeri F, Sessa F, Nannola C, Chisari MG, Cocimano G, Di Mauro L, Salerno M, Esposito M. Traumatic brain injury as a public health issue: Epidemiology, prognostic factors and useful data from forensic practice. Healthcare (Basel). 2024 Nov 13;12(22):2266. doi: 10.3390/healthcare12222266.
  2. Sirko A, Valadka AB,, Yadav G, Armonda R, Sköld M K. Neurosurgical management of combat-related penetrating traumatic brain injury – lessons from 10 years of war in Ukraine. Lakartidningen. 2025 Mar 13;122:24113. [Swedish].
  3. Woodrow RE, Menon DK, Stamatakis EA; CENTER-TBI MRI Sub-study Participants and Investigators. Repeat traumatic brain injury exacerbates acute thalamic hyperconnectivity in humans. Brain Commun. 2024 Jun 28;6(4):fcae223. doi: 10.1093/braincomms/fcae223.
  4. Chebotaryova LL, Kovalenko OE, Solonovych AS, Solo-novych OS. Posttraumatic stress disorder and mild traumatic brain injury – common consequences of war: issues of pathogenesis and differential diagnosis. Fam Med Eur Pract. 2023;2:64-72. [Ukrainian]. doi: 10.30841/2786- 720X.2.2023.282496. Вплив кверцетину на системну запальну відповідь і метаболізм за умов повторюваної легкої черепно-мозкової травми 27
  5. Boiko DI, Shyrai PO, Mats OV , Karpik ZI, Rahman MH, Khan AA, Alanazi AM, Skrypnikov AM. Mental health and sleep disturbances among Ukrainian refugees in the context of Russian-Ukrainian war: A preliminary result from online-survey. Sleep Med. 2024 Jan;113:342-8. doi: 10.1016/j.sleep.2023.12.004.
  6. May AC, Hendrickson RC, Pagulayan KF, Schindler AG. An observational cohort study of alcohol use and cognitive difficulties among post-9/11 veterans with and without TBI and PTSD. Drug Alcohol Depend. 2024 Oct 1;263:112419. doi: 10.1016/j.drugalcdep.2024.112419.
  7. Mayeux JP, Teng SX, Katz PS, Gilpin NW, Molina PE. Traumatic brain injury induces neuroinflammation and neuronal degeneration that is associated with escalated alcohol self-administration in rats. Behav Brain Res. 2015 Feb 15;279:22-30. doi: 10.1016/j.bbr.2014.10.053.
  8. Teng SX, Katz PS, Maxi JK, Mayeux JP, Gilpin NW, Molina PE. Alcohol exposure after mild focal traumatic brain injury impairs neurological recovery and exacerbates localized neuroinflammation. Brain Behav Immun. 2015 Mar;45:145-56. doi: 10.1016/j. bbi.2014.11.006.
  9. Zabenko YE, Atamas AV, Pivneva TA. Mild traumatic brain injury: general characteristics, neurodegenerative consequences and modeling. Fiziol Zh. 2017;63(3):80-9. [Ukrainian]. doi: 10.15407/fz63.03.080.
  10. Postolache TT, Wadhawan A, Can A, Lowry CA, Woodbury M, Makkar H, Hoisington AJ, Scott AJ, Potocki E, Benros ME, Stiller JW. Inflammation in Traumatic Brain Injury. J Alzheimers Dis. 2020;74(1):1- 28. doi: 10.3233/JAD-191150.
  11. Adamovych IM, Kostenko VO. Systemic inflamma-tory response and dysregulation of carbohydrate metabolism following mild repetitive traumatic brain injury in rats. Aktual Probl Suchasn Med: Visn Ukr Med Stomatol Akad. 2025;25(2):141-7. [Ukrainian]. doi: 10.31718/2077–1096.25.2.141.
  12. Korkmaz N, Kesikburun S, Atar MÖ, Sabuncu T. Insulin resistance and related factors in patients with moderate and severe traumatic brain injury. Ir J Med Sci. 2023 Jun;192(3):1177-82. doi: 10.1007/s11845-022-03147-y.
  13. Mykytenko AO, Akimov OYe, Yeroshenko GA, Nepo-rada KS. Influence of NF-κB on the development of oxidative-nitrosative stress in the liver of rats under conditions of chronic alcohol intoxication. Ukr Biochem J. 2022;94(6):57-66. doi: 10.15407/ubj94.06.057.
  14. Yelins'ka AM, Shvaykovs'ka OO, Kostenko VO. Epigal-locatechin-3-gallate prevents disruption of connective tissue in periodontium and salivary glands of rats during systemic inflammation. Wiad Lek. 2018;71(4):869-73.
  15. Frenkel Y , Cherno V , Kostenko H, Chopra H, Gautam RK, Kostenko V. Dietary supplementation with resveratrol attenuates serum melatonin level, pro-inflammatory response and metabolic disorder in rats fed high-fructose high-lipid diet under round-the-clock lighting. Pathophysiology. 2023 Feb; 30(1):37-47. doi: 10.3390/pathophysiology30010005.
  16. Yavtushenko IV , Nazarenko SM, Katrushov OV , Kostenko VO. Quercetin limits the progression of oxidative and nitrosative stress in the rats' tissues after experimental traumatic brain injury. Wiad Lek. 2020; 73(10):2127-32. doi: 10.36740/WLek202010104.
  17. Zyablitsev SV , Yelsky VM. Traumatic disease syndromes in traumatic brain injury. Kramatorsk: Kashtan; 2020. 264 p. [Ukrainian].
  18. Kozaeva R, Klymenko MO, Katrushov OV, Kostenko VO. Bioflavonoids as agents for correcting nitrooxidative stress and salivary gland functions in rats exposed to alcohol during modeled lipopolysaccharideinduced systemic inflammatory response. Wiad Lek. 2022;75(3):685-90. doi: 10.36740/WLek202203121.
  19. Antunes LC, Elkfury JL, Jornada MN, Foletto KC, Bertoluci MC. Validation of HOMA-IR in a model of insulin-resistance induced by a high-fat diet in Wistar rats. Arch Endocrinol Metab. 2016 Apr;60(2):138-42. doi: 10.1590/2359-3997000000169.
  20. Schültke E, Griebel RW, Juurlink BH. Quercetin administration after spinal cord trauma changes S-100 levels. Can J Neurol Sci. 2010 Mar;37(2):223-8. doi: 10.1017/s0317167100009963.
  21. Moybenko AA, editor. Bioflavonoids as organoprotectors (quercetin, corvitin, quertin). Kyiv: Naukova dumka; 2012.
  22. Kang CH, Choi YH, Moon SK, Kim WJ, Kim GY. Quercetin inhibits lipopolysaccharide-induced nitric oxide production in BV2 microglial cells by suppressing the NF-κB pathway and activating the Nrf2-dependent HO-1 pathway. Int Immunopharmacol. 2013 Nov;17(3):808-13. doi: 10.1016/j.intimp.2013.09.009.
  23. Chekalina NI, Kazakov YM, Mamontova TV , Vesnina LE, Kaidashev IP. Resveratrol more effectively than quercetin reduces endothelium degeneration and level of necrosis factor α in patients with coronary artery disease. Wiad Lek. 2016;69(3 pt 2):475-9.
  24. Opryshko V, Prokhach A, Akimov O, Riabushko M, Kostenko H, Kostenko V, Mishchenko A, Solovyova N, Kostenko V. Desmodium styracifolium: Botanical and ethnopharmacological insights, phytochemical investigations, and prospects in pharmacology and pharmacotherapy. Heliyon. 2024 Jan 20;10(3):e25058. doi: 10.1016/j.heliyon.2024.e25058.
  25. Aghababaei F, Hadidi M. Recent advances in potential health benefits of quercetin. Pharmaceuticals. 2023; 16(7):1020. doi: 10.3390/ph16071020.
  26. Lai JQ, Shi YC, Lin S, Chen XR. Metabolic disorders on cognitive dysfunction after traumatic brain injury. Trends Endocrinol Metab. 2022 Jul;33(7):451-62. doi: 10.1016/j. tem.2022.04.003.
  27. Li Z, Shen D, Meng Y , Xu H, Yuan H, Chen L. miR-155-5p alleviates ethanol-induced myocardial insulin resistance in H9C2 cells via regulating the mTOR signalling pathway. Mol Biol Rep. 2020 Dec;47(12):9469-77. doi: 10.1007/s11033-020-05967-6.
  28. Eid HM, Nachar A, Thong F, Sweeney G, Haddad PS. The molecular basis of the antidiabetic action of quercetin І.М. Адамович, Г.В. Костенко, О.Є. Акімов, В.О. Костенко 28 in cultured skeletal muscle cells and hepatocytes. Pharmacogn Mag. 2015 Jan-Mar;11(41):74-81. doi: 10.4103/0973-1296.
  29. Wang M, Wang B, Wang S, Lu H, Wu H, Ding M, Ying L, Mao Y , Li Y . Effect of quercetin on lipids metabolism through modulating the gut microbial and AMPK/ppar signaling pathway in broilers. Front Cell Dev Biol. 2021 Feb 9;9:616219. doi: 10.3389/fcell.2021.616219.
© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2026.