Журнал «Почки» Том 14, №3, 2025

Наявність багатьох спільних аспектів в авторегуляторних механізмах і процесах забезпечення сталості внутрішнього середовища зумовлює унікальність цереброренальної системи. Гамма-аміномасляній кислоті (ГАМК), окрім ключової координаторної ролі в активності мозку і його метаболізмі, притаманні регуляторні впливи в ненейрональних тканинах. Беручи до уваги те, що існує взаємозв’язок між рівнями ГАМК і функціональним та метаболічним станом інших органів і систем, метою роботи є зосередження уваги на наукових відомостях щодо локальних ГАМКергічних систем, розташування їхніх компонентів у нефроні та ренальних впливів ГАМК за різних умов. Поруч із тим, що ГАМК має терапевтичний потенціал проти гострого пошкодження і хронічної хвороби нирок, фармакологічні модулятори ГАМК можуть спровокувати нефротоксичність. Причини різноманітності ниркових реакцій під впливом ГАМК і агентів з агоністичною активністю мають багатофакторну природу, що слід брати до уваги, а в межах ГАМКергічних стратегій потрібно шукати та застосовувати ефективні й безпечні терапевтичні підходи.

The presence of many common aspects in autoregulatory mechanisms and processes of ensuring the constancy of the internal environment determines the uniqueness of the cerebro-renal system. Gamma-aminobutyric acid (GABA), in addition to the key coordinating role in brain activity and its metabolism, has inherent regulatory effects in non-neuronal tissues. Given the fact that there is a relationship between GABA levels and the functional and metabolic state of other organs and systems, the aim of the work is to focus on scientific information regarding local GABAergic systems, the location of their components in the nephron and the renal effects of GABA under different conditions. In addition to the fact that GABA has therapeutic potential against acute kidney injury and chronic kidney disease, pharmacological modulators of GABA can provoke nephrotoxicity. The reasons for the diversity of renal responses under the influence of GABA and agents with agonist activity are multifactorial in nature, which should be taken into account, and within the framework of GABAergic strategies, effective and safe therapeutic approaches should be sought and applied.

гамма-аміномасляна кислота; цереброренальна система; механізми взаємозв’язків

gamma-aminobutyric acid; cerebro-renal system; mechanisms of interrelationship

1. Tanaka S, Okusa MD. Crosstalk between the nervous system and the kidney. Kidney Int. 2020 Mar;97(3):466-476. doi: 10.1016/j.kint.2019.10.032.
2. Rajamani K. The Cerebro-Renal System — Anatomical and Physiological Considerations. J Stroke Cerebrovasc Dis. 2021 Sep;30(9):105541. doi: 10.1016/j.jstrokecerebrovasdis.2020.105541.
3. Ochoa-de la Paz LD, Gulias-Cañizo R, Ruíz-Leyja ED, Sánchez-Castillo H, Parodí J. The role of GABA neurotransmitter in the human central nervous system, physiology, and pathophysiology. Revista Mexicana de Neurociencia. 2021;22(2):67-76. doi: 10.24875/rmn.20000050.
4. Ngo DH, Vo TS. An Updated Review on Pharmaceutical Properties of Gamma-Aminobutyric Acid. Molecules. 2019 Jul 24;24(15):2678. doi: 10.3390/molecules24152678.
5. Jewett BE, Sharma S. Physiology, GABA. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513311/.
6. Ghit A, Assal D, Al-Shami AS, Hussein DEE. GABAA receptors: structure, function, pharmacology, and related disorders. J Genet Eng Biotechnol. 2021 Aug 21;19(1):123. doi: 10.1186/s43141-021-00224-0.
7. Kmet OG, Filipets ND, Kmet TI, Hrachova TI, Vepriuk YM, Vlasova KV. Pharmacological correction of cognitive disorders in experimental neurodegeneration caused by 2 type diabetes mellitus. Problems of Endocrine Pathology. 2019;70(4):52-59. doi: 10.21856/j-PEP.2019.4.07.
8. Sears SM, Hewett SJ. Influence of glutamate and GABA transport on brain excitatory/inhibitory balance. Exp Biol Med (Maywood). 2021 May;246(9):1069-1083. doi: 10.1177/1535370221989263.
9. Wan Y, Wang Q, Prud’homme GJ. GABAergic system in the endocrine pancreas: a new target for diabetes treatment. Diabetes Metab Syndr Obes. 2015 Feb 3;8:79-87. doi: 10.2147/DMSO.S50642.
10. Hagan DW, Ferreira SM, Santos GJ, Phelps EA. The role of GABA in islet function. Front Endocrinol (Lausanne). 2022 Sep 29;13:972115. doi: 10.3389/fendo.2022.972115.
11. Geisler CE, Ghimire S, Bruggink SM, Miller KE, Weninger SN, et al. A critical role of hepatic GABA in the metabolic dysfunction and hyperphagia of obesity. Cell Rep. 2021 Jun 29;35(13):109301. doi: 10.1016/j.celrep.2021.109301.
12. Yoshida K, Sunao S, Shingo T. Blood pressure-lowering effect of oral intake of gamma-minobutyric acid (GABA) — an updated systematic review with meta-analysis. Jpn Pharmacol Ther. 2024;52(8):901-926.
13. Bu J, Huang S, Wang J, Xia T, Liu H, et al. The GABA A Receptor Influences Pressure Overload-Induced Heart Failure by Modulating Macrophages in Mice. Front Immunol. 2021 May 31;12:670153. doi: 10.3389/fimmu.2021.670153.
14. Liang D, Zhou L, Zhou H, Zhang F, Fang G, et al. A –GABAergic system in atrioventricular node pacemaker cells controls electrical conduction between the atria and ventricles. Cell Res. 2024 Aug;34(8):556-571. doi: 10.1038/s41422-024-00980-x.
15. Wang Y, Liu S, Liu Q, Lv Y. The Interaction of Central Nervous System and Acute Kidney Injury: Pathophysiology and Clinical Perspectives. Front Physiol. 2022 Mar 4;13:826686. doi: 10.3389/fphys.2022.826686.
16. Nishihara M, Takesue K, Hirooka Y. Renal denervation enhances GABA-ergic input into the PVN leading to blood pressure lowering in chronic kidney disease. Auton Neurosci. 2017 May;204:88-97. doi: 10.1016/j.autneu.2016.09.018.
17. Kobuchi S, Tanaka R, Shintani T, Suzuki R, Tsutsui H, et al. Mechanisms underlying the renoprotective effect of GABA against ischaemia/reperfusion-induced renal injury in rats. Clin Exp Pharmacol Physiol. 2015 Mar;42(3):278-86. doi: 10.1111/1440-1681.
18. Milanez MIO, Veiga AC, Martins BS, Pontes RB, Bergama–schi CT, et al. Renal Sensory Activity Regulates the γ-Aminobutyric Acidergic Inputs to the Paraventricular Nucleus of the Hypothalamus in Goldblatt Hypertension. Front Physiol. 2020 Dec 15;11:601237. doi: 10.3389/fphys.2020.601237.
19. Filipets N, Gozhenko A, Ivanov D, Filipets O, Gabunia L. Regulatory mechanisms for maintaining homeostasis of sodium ions. Kidneys. 2022;11(3):175-180. doi: 10.22141/2307-1257.11.3.2022.378.
20. Filipets ND, Ivanov DD, Gozhenko AI. Renin-angiotensin-aldosterone system blockers as the main pathogenetic approach of drug nephroprotection. Kidneys. 2019;8(1):34-39. doi: 10.22141/2307-1257.8.1.2019.157794.
21. Filipets ND. Local renin-angiotensin system in cerebro-renal continuum (review). Аctual Problems of Transport Medicine. 2019;1(55):41-47. doi: 10.5281/zenodo.2612929.
22. Li DP, Pan HL. Angiotensin II attenuates synaptic GABA release and excites paraventricular-rostral ventrolateral medulla output neurons. J Pharmacol Exp Ther. 2005 Jun;313(3):1035-45. doi: 10.1124/jpet.104.082495.
23. Chen HH, Cheng PW, Ho WY, et al. Renal Denervation Improves the Baroreflex and GABA System in Chronic Kidney Di–sease-induced Hypertension. Sci Rep. 2016;6:38447. doi: 10.1038/srep38447.
24. Gozhenko AI. Theory of disease: monograph. Odessa: Phoenix; 2017. 236 p.
25. Párducz A, Dobó E, Wolff JR, Petrusz P, Erdö SL. GABA-immunoreactive structures in rat kidney. J Histochem Cytochem. 1992 May;40(5):675-80. doi: 10.1177/40.5.1573248.
26. Takano K, Yatabe MS, Abe A, Suzuki Y, Sanada H, et al. Characteristic expressions of GABA receptors and GABA produ–cing/transporting molecules in rat kidney. PLoS One. 2014 Sep 4;9(9):e105835. doi: 10.1371/journal.pone.0105835.
27. Ogobuiro I, Tuma F. Physiology, Renal. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538339/.
28. Pivovarov AS, Calahorro F, Walker RJ. Na+/K+-pump and neurotransmitter membrane receptors. Invert Neurosci. 2018 Nov 28;19(1):1. doi: 10.1007/s10158-018-0221-7.
29. Wildman SS, Dunn K, Van Beusecum JP, Inscho EW, Kelley S, et al. A novel functional role for the classic CNS neurotransmitters, GABA, glycine, and glutamate, in the kidney: potent and oppo–sing regulators of the renal vasculature. Am J Physiol Renal Physiol. 2023 Jul 1;325(1):F38-F49. doi: 10.1152/ajprenal.00425.2021.
30. Lee H, Ji SY, Hwangbo H, Kim MY, Kim DH, et al. Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced Nephrotoxi–city. Int J Mol Sci. 2022 Jan 3;23(1):502. doi: 10.3390/ijms23010502.
31. Kim HY, Yokozawa T, Nakagawa T, Sasaki S. Protective effect of gamma-aminobutyric acid against glycerol-induced acute renal failure in rats. Food Chem Toxicol. 2004 Dec;42(12):2009-14. doi: 10.1016/j.fct.2004.06.021.
32. Huang HY, Hsu T, Lin BF. Gamma-aminobutyric acid decreases macrophages infiltration and suppresses inflammatory responses in renal injury. Journal of Functional Foods. 2019;60:103419. doi: 10.1016/j.jff.2019.103419.
33. Madbouly N, Ooda A, Nabil A, Nasser A, Ahmed E, Ali F, et al. The renoprotective activity of amikacin-gamma-amino butyric acid-chitosan nanoparticles: a comparative study. Inflammopharmacology. 2024 Aug;32(4):2629-2645. doi: 10.1007/s10787-024-01464-5.
34. Su R, Chang L, Zhou T, Meng F, Zhang D. Effects of GABA on Oxidative Stress and Metabolism in High-Glucose Cultured Mongolian Sheep Kidney Cells. Int J Mol Sci. 2024 Sep 18;25(18):10033. doi: 10.3390/ijms251810033.
35. Kmet OG, Filipets ND, Rohovyi YuYe, Hrachova TI, Vepriuk YM, Vlasova KV. Assessment of carbacetam effect with cerebral mitochondrial dysfunction of rats with type 2 diabetes mellitus. Problems of Endocrine Pathology. 2020;73(3):16-24. doi: 10.21856/j-PEP.2020.3.02.
36. Kmet O, Filipets N, Yaremii I, Kmet T, Vepriuk Y, Hrachova T. Experimental assessment of carbacetam effect on the cerebral mitochondria under conditions of scopalamine-induced Alzheimer’s disease. Arch Balk Med Union. 2020;55(1):14-21. doi: 10.31688/ABMU.2020.54.5.01.
37. Gai Z, Gui T, Kullak-Ublick GA, Li Y, Visentin M. The Role of Mitochondria in Drug-Induced Kidney Injury. Front Physiol. 2020 Sep 4;11:1079. doi: 10.3389/fphys.2020.01079.
38. Su L, Zhang J, Gomez H, Kellum JA, Peng Z. Mitochondria ROS and mitophagy in acute kidney injury. Autophagy. 2022;19(2):401-414. doi: 10.1080/15548627.2022.2084862.
39. El-Dessouki AM, Alzokaky AA, Raslan NA, Ibrahim S, Sa–lama LA, Yousef EH. Piracetam mitigates nephrotoxicity induced by cisplatin via the AMPK-mediated PI3K/Akt and MAPK/JNK/ERK signaling pathways. Int Immunopharmacol. 2024 Aug 20;137:112511. doi: 10.1016/j.intimp.2024.112511.
40. He Y, Mo L, Li J, Lu D, Niu J, et al. Association of perio–perative initiation of gabapentin versus pregabalin with kidney function: a target trial emulation study. Front Med (Lausanne). 2024 Dec 10;11:1488773. doi: 10.3389/fmed.2024.1488773.
41. Zhang M, Huang L, Zhu Y, et al. Diazepam exposure associated with an increased risk of acute kidney injury in children: an observational cohort study. BMC Pediatr. 2025;25:159. doi: 10.1186/s12887-025-05494-y.
42. Anguissola G, Leu D, Simonetti GD, et al. Kidney tubular injury induced by valproic acid: systematic literature review. Pediatr Nephrol. 2023;38:1725-173. doi: 10.1007/s00467-022-05869-8.
43. Reddy DS. Neurosteroids as Novel Anticonvulsants for Refractory Status Epilepticus and Medical Countermeasures for Nerve Agents: A 15-Year Journey to Bring Ganaxolone from Bench to Clinic. J Pharmacol Exp Ther. 2024 Jan 17;388(2):273-300. doi: 10.1124/jpet.123.001816.