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The Effects of Xenon on GSK-3β, NF-κB, and Nrf2 Levels in the Rat Brain: An Experimental Study

https://doi.org/10.15360/1813-9779-2025-3-2563

Abstract

Aim. To evaluate the impact of subanesthetic concentrations of xenon on the brain levels of GSK-3β, NF-κB, and Nrf2 in intact rats.

Materials and Methods. Male laboratory rats were randomly assigned to three groups (N=5 per group): the control group received inhalation of a nitrogen-oxygen gas mixture; the Xe-70 group received 70% xenon; and the Xe-35 group received 35% xenon. Following euthanasia, brain tissue samples were analyzed using Western blotting and densitometric quantification to assess levels of phosphorylated GSK-3β, NF-κB, and Nrf2. Results. Inhalation of xenon-oxygen mixtures led to a statistically significant increase in phosphorylated GSK-3β levels in both the Xe-70 group (95% CI: 593,723–1,018,826; P=0.0001; R=0.72) and the Xe-35 group (95% CI: 458,413–872,807; P=0.0001; R=0.80), compared with controls. Xenon exposure also resulted in a significant reduction in NF-κB levels in the Xe-70 (95% CI: 205,138–601,617; P=0.0005; R=0.95) and Xe-35 (95% CI: 217,700–608,462; P=0.0003; R=0.95) groups. Furthermore, Nrf2 protein expression was significantly elevated in the Xe-35 group compared to controls (95% CI: 260,926–692,532; P=0.0002; R=0.91).

Conclusion. Subanesthetic xenon concentrations exert a significant modulatory effect on GSK-3β, NF-κB, and Nrf2 expression in the brain tissue of intact rats.

About the Authors

E. E. Beda
V. A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Russian Federation

Evgeniy E. Beda

25 Petrovka Str., Bldg. 2, 107031 Moscow



M. V. Gabitov
V. A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Russian Federation

Mikhail V. Gabitov

25 Petrovka Str., Bldg. 2, 107031 Moscow



I. V. Redkin
V. A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Russian Federation

Ivan V. Redkin

25 Petrovka Str., Bldg. 2, 107031 Moscow



I. A. Kryukov
V. A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Russian Federation

Ivan A. Kryukov

25 Petrovka Str., Bldg. 2, 107031 Moscow



O. A. Grebenchikov
V. A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Russian Federation

Oleg A. Grebenchikov

25 Petrovka Str., Bldg. 2, 107031 Moscow



References

1. Mousavikia S. N., Darvish L., Firouzjaei A. A., Toossi M. T. B., Azimian H. J. PI3K/AKT/mTOR targeting in colorectal cancer radiotherapy: a systematic review. Gastrointest Cancer. 2025; 56 (1): 52. DOI: 10.1007/s12029-024-01160-1. PMID: 39849185.

2. Park J. I. MAPK-ERK pathway. Int J Mol Sci. 2023; 24 (11): 9666. DOI: 10.3390/ijms24119666. PMID: 37298618.

3. Iluta S., Nistor M., Buruiana S., Dima D. Wnt signaling pathway in tumor biology. Genes (Basel). 2024; 15 (12): 1597. DOI: 10.3390/genes15121597. PMID: 39766864.

4. Hu Q., Bian Q., Rong D., Wang L., Song J., Huang H. S., Zeng J., et al. JAK/STAT pathway: extracellular signals, diseases, immunity, and therapeutic regimens. Front Bioeng Biotechnol. 2023; 11: 1110765. DOI: 10.3389/fbioe.2023.1110765. eCollection 2023. PMID: 36911202.

5. Ostrova I. V., Grebenchikov O. A., Golubeva N. V. Neuroprotective effect of lithium chloride in rat model of cardiac arrest. General Reanimatology= Obshchaya Reanimatologiya. 2019; 15 (3): 73–82. (in Russ.&Eng.). DOI: 10.15360/1813-9779-2019-3-73-82.

6. Zhang J., Yang S. G., Zhou F. Q. Glycogen synthase kinase 3 signaling in neural regeneration in vivo. J Mol Cell Biol. 2024; 15 (12): mjad075. DOI: 10.1093/jmcb/mjad075. PMID: 38059848.

7. Saha S., Buttari B., Panieri E., Profumo E., Saso L. An overview of Nrf2 signaling pathway and its role in inflammation. Molecules. 2020; 25 (22): 5474. DOI: 10.3390/molecules25225474. PMID: 33238435.

8. Shilovsky G. A., Sorokina E. V., Orlovsky I. V. Transcription factor NRF2 — a target of potential antioxidant drugs: prospects in treatment of age–related diseases. Clinical Gerontology= Klinicheskaya Gerontologiya. 2021; 27 (11–12): 57–62. (in Russ.). DOI: 10.26347/1607-2499202111-12057-062.

9. Barnabei L., Laplantine E., Mbongo W., Rieux-Laucat F., Weil R. NF-kappaB: at the borders of autoimmunity and inflammation. Front Immunol. 2021; 12: 716469. DOI: 10.3389/fimmu.2021.716469. PMID: 34434197

10. Boeva E. A., Grebenchikov O. A. Organoprotective properties of argon (review). General Reanimatology = Obshchaya Reanimatologiya. 2022; 18 (5): 44–59. (in Russ.&Eng.). DOI: 10.15360/1813-9779-2022-5-44-59.

11. Kaufman M. J., Meloni E. G. Xenon gas as a potential treatment for opioid use disorder, alcohol use disorder, and related disorders. Med Gas Res. 2025; 15 (2): 234–253. DOI: 10.4103/mgr.MEDGASRES-D-24-00063. PMID: 39812023.

12. Antonova V. V., Silachev D. N., Plotnikov E. Y., Pevzner I. B., Yakupova E. I., Pisarev M. V., Boeva E. A., et al. Neuroprotective effects of krypton inhalation on photothrombotic ischemic stroke. Biomedicines. 2024; 12 (3): 635. DOI: 10.3390/biomedicines12030635. PMID: 38540249.

13. Grebenchikov O. A., Molchanov I. V., Shpichko A. I., Evseev A. K., Shabanov A. K., Khusainov S. Z., Petrikov S. S. Neuroprotective properties of xenon according to experimental studies. Russian Sklifosovsky Journal «Emergency Medical Care» = Zhurnal im. N. V. Sklifosovskogo «Neotlozhnaya Meditsinskaya Pomoshch». 2020; 9 (1): 85–95. (in Russ.). DOI:10.23934/2223-9022-2020-9-l-85-95.

14. Beda E. E., Gabitov M. V., Grebenchikov O. A. The effect of xenon in various concentrations on the volume of brain damage and severity of neurological disorders in rat model of open traumatic brain injury. Pathological Physiology and Experimental Therapy = Patologicheskaya Fiziologiya i Exsperimentalnaya Terapiya. 2024; 68 (1): 26-36. (in Russ.). DOI: 10.25557/0031-2991.2024.01.26-36.

15. Shpichko A. I., Grebenchikov O. A., Molchanov I. V., Shabanov A. K., Shpichko N. P., Kadantseva K. K. Cardioprotective properties of xenon. Russian Sklifosovsky Journal «Emergency Medical Care» = Zhurnal im. N. V. Sklifosovskogo «Neotlozhnaya Meditsinskaya Pomoshch». 2020; 9 (2): 266–271. (in Russ.). DOI: 10.23934/2223-9022-2020-9-2-96-107.

16. Nakata Y., Goto T., Ishiguro Y., Terui K., Kawakami H., Santo M., Niimi Y., et al. Minimum alveolar concentration (MAC) of xenon with sevoflurane in humans. J Am Soc Anesthesiol. 2001; 94 (4): 611–614. DOI: 10.1097/00000542-200104000-00014. PMID: 11379681.

17. Cullen S. C., Eger E. D. II, Cullen B. F., Gregory P. Observations on the anesthetic effect of the combination of xenon and halothane. Anesthesiology. 1969; 31: 305-30. DOI: 10.1097/00000542-196910000-00003. PMID: 5811596.

18. Koblin D. D., Fang Z., Eger E. I., Laster M. J., Gong D., Ionescu P., Halsey M. J., et al. Minimum alveolar concentrations of noble gases, nitrogen, and sulfur hexafluoride in rats: helium and neon as nonimmobilizers (nonanesthetics). Anesth Analg. 1998; 87 (2): 419–424. DOI: 10.1213/00000539-199808000-00035. PMID: 9706943.

19. Politov M. E., Podprugina S. V., Zolotova E. N., Nogtev P. V., Agakina Yu. S., Zhukova S. G., Yavorovsky A. G. Clinical application of xenon in subanesthetic concentrations (review). General Reanimatology = Obshchaya Reanimatologiya. 2025; 21 (2): 55–67. (in Russ&Eng.). DOI: 10.15360/1813-9779-2025-2-2554.

20. Veldeman M., Coburn M., Rossaint R., Clusmann H., Nolte K., Kremer B., Höllig A. Xenon reduces neuronal hippocampal damage and alters the pattern of microglial activation after experimental subarachnoid hemorrhage: a randomized controlled animal trial. Front Neurol. 2017; 8: 511. DOI: 10.3389/fneur.2017.00511. PMID: 29021779.

21. Amer A. R., Oorschot D. E. Xenon combined with hypothermia in perinatal hypoxic-ischemic encephalopathy: a noble gas, a noble mission. Pediatr Neurol. 2018; 84: 5–10. DOI: 10.1016/j.pediatrneurol.2018.02.009. PMID: 29887039.

22. Campos-Pires R., Onggradito H., Ujvari E., Karimi S., Valeo F., Aldhoun J., Edge C. J., et al. Xenon treatment after severe traumatic brain injury improves locomotor outcome, reduces acute neuronal loss and enhances early beneficial neuroinflammation: a randomized, blinded, controlled animal study. Crit Care. 2020; 24: 667. DOI: 10.1186/s13054-020-03373-9. PMID: 33246487.

23. Hollmén C., Parkkola R., Vorobyev V., Saunavaara J., Laitio R., Arola O., Hynninen M., et al. Neuroprotective effects of inhaled xenon gas on brain structural gray matter changes after out-ofhospital cardiac arrest evaluated by morphometric analysis: a substudy of the randomized xe-hypotheca trial. Neurocrit Care. 2025; 42 (1): 131–141. DOI: 10.1007/s12028-024-02053-8. PMID: 38982000.

24. Brandao W., Jain N., Yin Z., Kleemann K. L., Carpenter M., Bao X., Serrano J. R., et al. Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy. Sci Transl. Med. 2025; 17 (781): eadk3690. DOI: 10.1126/scitranslmed.adk3690. PMID: 39813317.

25. Filev A. D., Silachev D. N., Ryzhkov I. A., Lapin K. N., Babkina A. S., Grebenchikov O. A., Pisarev V. M. Effect of xenon treatment on gene expression in brain tissue after traumatic brain injury in rats. Brain Sci. 2021; 11 (7): 889. DOI: 10.3390/brainsci11070889. PMID: 34356124.

26. Kabiolsky I. A., Simonenko S. D., Sarycheva N.Yu., Dubynin V. A. Therapeutic effects of inert gases. I. M. Sechenov Russian Journal of Physiology = Ross. Fiziol. Zh. Im. I. M. Sechenova. 2024; 110 (10): 1582–1601. (in Russ.). DOI: 10.31857/S0869813924100033.

27. Grebenchikov O. A., Avrushchenko M. Sh., Borisov K.Yu., Ilyin Yu.V., Likhvantsev V. V. Neuroprotective effects of sevoflurane on a total ischemia-reperfusion model. Clinical Pathophysiology / Klinicheskaya Patofysiologiya. (in Russ.). 2014; 2: 57–62.

28. Ruiz S. A., Rippin I., Eldar-Finkelman H. Prospects in GSK-3 signaling: from cellular regulation to disease therapy. Cells. 2022; 11 (10): 1618. DOI: 10.3390/cells11101618. PMID: 35626655.

29. Ershov A. V., Krukov I. A., Antonova V. V., Baeva A. A. The effect of xenon on the activity of glycogen synthase kinase-3b in the perifocal zone of ischemic cerebral infarction (experimental study). General Reanimatology = Obshchaya Reanimatologiya. 2023; 19 (2): 60–67. (in Russ.&Eng.). DOI: 10.15360/1813-9779-2023-2-2274.

30. Li Y., Chu L, Liu C., Zha Z., Shu Y. Protective effect of GSK-3β/Nrf2 mediated by dimethyl fumarate in middle cerebral artery embolization reperfusion rat model. Curr Neurovasc Res. 2021; 18 (4): 456–464. DOI: 10.2174/1567202618666211109105024. PMID: 34751118.

31. Niu Q., Sun W., Chen Q., Long Y., Cao W., Wen S., Li A., et al. Protective effects of ischemic postconditioning on livers in rats with limb ischemia-reperfusion via glycogen synthase kinase 3 beta (GSK-3β)/fyn/nuclear receptor-erythroid-2-related factor (Nrf2) pathway. Med Sci Monit. 2020; 26. DOI: 10.12659/MSM.923049. PMID: 32686659.

32. Yu H., Lin L., Zhang Z., Zhang H., Hu H. Targeting NF-kappaB pathway for the therapy of diseases: mechanism and clinical study. Signal Transduct Target Ther. 2020; 5 (1): 209. DOI: 10.1038/s41392-020-00312-6. PMID: 32958760.

33. Yang S. R., Hua K. F., Chu L. J., Hwu Y. K., Yang S. M., Wu C. Y., Lin T. J., et al. Xenon blunts NF-kappaB/NLRP3 inflammasome activation and improves acute onset of accelerated and severe lupus nephritis in mice. Kidney Int. 2020; 98 (2): 378–390. DOI: 10.1016/j.kint.2020.02.033. PMID: 32622527.

34. Zhao H., Huang H., Ologunde R., Lloyd D. G., Watts H., Vizcaychipi M. P., Lian Q., et al. Xenon treatment protects against remote lung injury after kidney transplantation in rats. Anesthesiology. 2015; 122: 1312–26. DOI: 10.1097/ALN.0000000000000664. PMID: 25856291.


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For citations:


Beda E.E., Gabitov M.V., Redkin I.V., Kryukov I.A., Grebenchikov O.A. The Effects of Xenon on GSK-3β, NF-κB, and Nrf2 Levels in the Rat Brain: An Experimental Study. General Reanimatology. 2025;21(3):26-31. (In Russ.) https://doi.org/10.15360/1813-9779-2025-3-2563

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ISSN 1813-9779 (Print)
ISSN 2411-7110 (Online)