Glutathione: a key molecule of redox homeostasis and its potential for nutritional and metabolic regulation. a review of the literature

封面
  • 作者: Shrayner E.V.1,2,3,4, Bystrova V.I.1,2, Pokushalov E.A.3,4, Romanova A.D.5, Markin D.S.1, Kudlay D.A.1,6,7
  • 隶属关系:
    1. Federal State Autonomous Educational Institution of Higher Education “Novosibirsk National Research State University”
    2. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences
    3. State Corporation “Center for New Medical Technologies”
    4. “Soloways” Laboratory
    5. Federal State Educational Institution of Higher Education “Murmansk Arctic University”
    6. Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
    7. Federal State Budget Educational Institution of Higher Education M.V. Lomonosov Moscow State University
  • 期: 卷 23, 编号 5 (2025)
  • 页面: 79-88
  • 栏目: Reviews
  • URL: https://journals.eco-vector.com/1728-2918/article/view/696275
  • DOI: https://doi.org/10.29296/24999490-2025-05-09
  • ID: 696275

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详细

Introduction. Glutathione (GSH) is a key intracellular antioxidant involved in maintaining redox homeostasis, detoxifying xenobiotics, regulating immune and neurotransmitter systems, and supporting protein folding and degradation. Depletion of GSH is associated with numerous chronic conditions, including neurodegenerative and metabolic disorders, cancer, liver diseases, HIV infection, and cardiovascular pathologies.

Objective. To summarize and systematize modern scientific data on the role of glutathione (GSH) as a key molecule in maintaining redox homeostasis in the body, and to study the existing possibilities of nutrient and metabolic regulation of its synthesis and metabolism.

Results. This review summarizes the molecular mechanisms of GSH synthesis and recycling, focusing on the role of enzymatic systems (e.g., GST, GGT, GCL), genetic polymorphisms, nutritional status, and amino acid availability (notably cysteine, glutamine, glycine, serine, and taurine). Special attention is given to nutrient-based interventions to restore GSH levels using precursors such as N-acetylcysteine (NAC), S-adenosylmethionine (SAMe), and oxothiazolidine derivatives (OTC). The bioavailability and effectiveness of different GSH delivery forms–oral, sublingual, liposomal, and intravenous–are discussed in the context of oxidative stress and disease. The review highlights the importance of integrating genetic profiling, nutrient intake, and redox biomarkers to personalize GSH-targeted therapeutic strategies.

Conclusion. Glutathione is a key molecule in antioxidant, metabolic, and immune defense. Disturbances in its metabolism, caused by external and internal factors, are associated with the development of chronic diseases. The use of glutathione and its precursors (NAC, glycine, etc.) holds promise for nutritional support in GSH deficiency, but requires further clinical study. Nutrigenetics and redox status assessment allow for personalized correction of glutathione metabolism and increased effectiveness of antioxidant therapy.

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作者简介

Evgenia Shrayner

Federal State Autonomous Educational Institution of Higher Education “Novosibirsk National Research State University”; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences; State Corporation “Center for New Medical Technologies”; “Soloways” Laboratory

编辑信件的主要联系方式.
Email: sch704@icloud.com
ORCID iD: 0000-0003-3606-4068

Associate Professor, Research Fellow, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Research Fellow, Gastroenterologist, Pediatrician, Candidate of Medical Sciences

俄罗斯联邦, Pirogova str., 1, Novosibirsk, 630090; Akademika Lavrentyeva str., 8, Novosibirsk, 630090; Pirogova Str., 25/4, Novosibirsk, 630090; Trudovaya str., 3, Novosibirsk, 630099

Valeria Bystrova

Federal State Autonomous Educational Institution of Higher Education “Novosibirsk National Research State University”; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Email: Valeria.bystrova.00@mail.ru
ORCID iD: 0000-0003-3522-5384

Resident Physician, Researcher

俄罗斯联邦, Pirogova str., 1, Novosibirsk, 630090; Akademika Lavrentyeva str., 8, Novosibirsk, 630090

Evgeny Pokushalov

State Corporation “Center for New Medical Technologies”; “Soloways” Laboratory

Email: E.pokushalov@gmail.com
ORCID iD: 0000-0002-9494-4234

Corresponding Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Deputy Director for Science, Deputy Director for Science, “Soloways” Laboratory

俄罗斯联邦, Pirogova Str., 25/4, Novosibirsk, 630090; Trudovaya str., 3, Novosibirsk, 630099

Anastasia Romanova

Federal State Educational Institution of Higher Education “Murmansk Arctic University”

Email: nova-roma@mail.ru

Student

俄罗斯联邦, Sportivnaya str., 13, Murmansk, 183010

Denis Markin

Federal State Autonomous Educational Institution of Higher Education “Novosibirsk National Research State University”

Email: deeesik@gmail.com
ORCID iD: 0009-0006-6845-1686

Resident Physician

俄罗斯联邦, Pirogova str., 1, Novosibirsk, 630090

Dmitry Kudlay

Federal State Autonomous Educational Institution of Higher Education “Novosibirsk National Research State University”; Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University); Federal State Budget Educational Institution of Higher Education M.V. Lomonosov Moscow State University

Email: D624254@gmail.com
ORCID iD: 0000-0003-1878-4467

Corresponding Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor of the Department of Pharmacology, Institute of Pharmacy, Professor of the Department of Pharmacognosy and Industrial Pharmacy, Faculty of Fundamental Medicine, Director of Innovative Development Programs

俄罗斯联邦, Pirogova str., 1, Novosibirsk, 630090; Trubetskaya str., 8, build. 2, Moscow, 119991; Leninskie Gory, 1, Moscow, 119991

参考

  1. Pérez L.M., Hooshmand B., Mangialasche F., Mecocci P., Smith A.D., Refsum H., Inzitari M., Fratiglioni L., Rizzuto D., Calderón-Larrañaga A. Glutathione Serum Levels and Rate of Multimorbidity Development in Older Adults. J. Gerontol A Biol Sci Med Sci. 2020; 75 (6): 1089–94. doi: 10.1093/gerona/glz101.
  2. Park S.A., Byeon G., Jhoo J.H., Kim H.C. et al. A Preliminary Study on the Potential Protective Role of the Antioxidative Stress Markers of Cognitive Impairment: Glutathione and Glutathione Reductase. Clin Psychopharmacol Neurosci. 2023; 21 (4): 758–68. doi: 10.9758/cpn.23.1053.
  3. Marengo B., Pulliero A., Izzotti A., Domenicotti C. miRNA Regulation of Glutathione Homeostasis in Cancer Initiation, Progression and Therapy Resistance. Microrna. 2020; 9 (3): 187–97. doi: 10.2174/2211536609666191218103220.
  4. Tan H.K., Yates E., Lilly K., Dhanda A.D. Oxidative stress in alcohol-related liver disease. World J. Hepatol. 2020; 12 (7): 332–49. doi: 10.4254/wjh.v12.i7.332.
  5. Aoyama K. Glutathione in the Brain. Int. J. Mol. Sci. 2021; 22 (9): 5010. doi: 10.3390/ijms22095010.
  6. Dickerhof N., Pearson J.F., Hoskin T.S., Berry L.J. et al. Oxidative stress in early cystic fibrosis lung disease is exacerbated by airway glutathione deficiency. Free Radic Biol Med. 2017; 113: 236–43. doi: 10.1016/j.freeradbiomed.2017.09.028.
  7. Achari A.E., Jain S.K. l-Cysteine supplementation increases insulin sensitivity mediated by upregulation of GSH and adiponectin in high glucose treated 3T3-L1 adipocytes. Arch Biochem Biophys. 2017; 630: 54–65. doi: 10.1016/j.abb.2017.07.016.
  8. Nguyen D., Hsu J.W., Jahoor F., Sekhar R.V. Effect of increasing glutathione with cysteine and glycine supplementation on mitochondrial fuel oxidation, insulin sensitivity, and body composition in older HIV-infected patients. J. Clin. Endocrinol Metab. 2014; 99 (1): 169–77. doi: 10.1210/jc.2013-2376.
  9. Robaczewska J., Kedziora-Kornatowska K., Kozakiewicz M. et al. Role of glutathione metabolism and glutathione-related antioxidant defense systems in hypertension. J. Physiol Pharmacol. 2016; 67 (3): 331–7.
  10. Gould R.L., Pazdro R. Impact of Supplementary Amino Acids, Micronutrients, and Overall Diet on Glutathione Homeostasis. Nutrients. 2019; 11 (5): 1056. doi: 10.3390/nu11051056.
  11. Marcus S.R., Chandrakala M.V., Nadiger H.A. Interaction between vitamin E and glutathione in rat brain: Effect of chronic ethanol administration. Asia Pac J. Clin. Nutr. 1998; 7 (3/4): 201–5.
  12. Sharma A., Kharb S., Chugh S.N., Kakkar R., Singh G.P. Effect of glycemic control and vitamin E supplementation on total glutathione content in non-insulin-dependent diabetes mellitus. Ann Nutr Metab. 2000; 44 (1): 11–3. doi: 10.1159/000012815.
  13. Kayan M., Naziroğlu M., Celik O., Yalman K., Köylü H. Vitamin C and E combination modulates oxidative stress induced by X-ray in blood of smoker and nonsmoker radiology technicians. Cell Biochem Funct. 2009; 27 (7): 424–9. doi: 10.1002/cbf.1589.
  14. Anand S.S. Protective effect of vitamin B6 in chromium-induced oxidative stress in liver. J. Appl Toxicol. 2005; 25 (5): 440–3. doi: 10.1002/jat.1077.
  15. Otero-Losada M., Vila S., Azzato F., Milei J. Antioxidants supplementation in elderly cardiovascular patients. Oxid Med Cell Longev. 2013; 2013: 408260. doi: 10.1155/2013/408260.
  16. Hsu C.C., Cheng C.H., Hsu C.L., Lee W.J. et al. Role of vitamin B6 status on antioxidant defenses, glutathione, and related enzyme activities in mice with homocysteine-induced oxidative stress. Food Nutr Res. 2015; 59: 25702. doi: 10.3402/fnr.v59.25702.
  17. Mahfouz M.M., Kummerow F.A. Vitamin C or Vitamin B6 supplementation prevent the oxidative stress and decrease of prostacyclin generation in homocysteinemic rats. Int J. Biochem Cell Biol. 2004; 36 (10): 1919–32. doi: 10.1016/j.biocel.2004.01.028.
  18. Chatzakis C., Sotiriadis A., Tsakmaki E., Papagianni M., Paltoglou G., Dinas K., Mastorakos G. The Effect of Dietary Supplements on Oxidative Stress in Pregnant Women with Gestational Diabetes Mellitus: A Network Meta-Analysis. Nutrients. 2021; 13 (7): 2284. doi: 10.3390/nu13072284.
  19. Bradbury J., Wilkinson S., Schloss J. Nutritional Support During Long COVID: A Systematic Scoping Review. J. Integr Complement Med. 2023; 29 (11): 695–704. doi: 10.1089/jicm.2022.0821.
  20. Duffy S.L., Lagopoulos J., Cockayne N., Lewis S.J. et al. The effect of 12-wk ω-3 fatty acid supplementation on in vivo thalamus glutathione concentration in patients «at risk» for major depression. Nutrition. 2015; 31 (10): 1247–54. doi: 10.1016/j.nut.2015.04.019.
  21. Taş S., Sarandöl E., Dirican M. Vitamin B6 supplementation improves oxidative stress and enhances serum paraoxonase/arylesterase activities in streptozotocin-induced diabetic rats. Scientific World J. 2014; 2014: 351598. doi: 10.1155/2014/351598.
  22. Cheng S.B., Lin P.T., Liu H.T., Peng Y.S. et al. Vitamin B-6 Supplementation Could Mediate Antioxidant Capacity by Reducing Plasma Homocysteine Concentration in Patients with Hepatocellular Carcinoma after Tumor Resection. Biomed Res Int. 2016; 2016: 7658981. doi: 10.1155/2016/7658981.
  23. DiFrancisco-Donoghue J., Lamberg E.M., Rabin E., Elokda A. et al. Effects of exercise and B vitamins on homocysteine and glutathione in Parkinson’s disease: a randomized trial. Neurodegener Dis. 2012; 10 (1–4): 127–34. doi: 10.1159/000333790.
  24. Conklin P.L., Foyer C.H., Hancock R.D., Ishikawa T., Smirnoff N. Ascorbic acid metabolism and functions. J. Exp. Bot. 2024; 75 (9): 2599–603. doi: 10.1093/jxb/erae143.
  25. Morelli M.B., Gambardella J., Castellanos V., Trimarco V., Santulli G. Vitamin C and Cardiovascular Disease: An Update. Antioxidants (Basel). 2020; 9 (12): 1227. doi: 10.3390/antiox9121227.
  26. Lal H., Chugh K., Saini V. et al. Effect of methionine and vitamin C supplementation on pulmonary glutathione-s-transferase and glutathione levels in ageing rats. Indian J. Clin. Biochem. 1993; 8: 33–5. doi: 10.1007/BF02867720.
  27. Lee E., Park H.Y., Kim S.W., Kim J., Lim K. Vitamin C and glutathione supplementation: a review of their additive effects on exercise performance. Phys Act Nutr. 2023; 27 (3): 36–43. doi: 10.20463/pan.2023.0027.
  28. Lenton K.J., Sané A.T., Therriault H., Cantin A.M., Payette H., Wagner J.R. Vitamin C augments lymphocyte glutathione in subjects with ascorbate deficiency. Am. J. Clin. Nutr. 2003; 77 (1): 189–95. doi: 10.1093/ajcn/77.1.189.
  29. Malik A., Bagchi A.K., Vinayak K., Akolkar G. et al. Vitamin C: historical perspectives and heart failure. Heart Fail Rev. 2021; 26 (3): 699–709. doi: 10.1007/s10741-020-10036-y. Epub 2020 Oct 8. Erratum in: Heart Fail Rev. 2021; 26 (2): 451. doi: 10.1007/s10741-020-10043-z.
  30. Zal F., Mostafavi-Pour Z., Amini F., Heidari A. Effect of vitamin E and C supplements on lipid peroxidation and GSH-dependent antioxidant enzyme status in the blood of women consuming oral contraceptives. Contraception. 2012; 86 (1): 62–6. doi: 10.1016/j.contraception.2011.11.006.
  31. Lubos E., Loscalzo J., Handy D.E. Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal. 2011; 15 (7): 1957–97. doi: 10.1089/ars.2010.3586.
  32. Ghasemzadeh Rahbardar M., Cheraghi Farmad H., Hosseinzadeh H., Mehri S. Protective effects of selenium on acrylamide-induced neurotoxicity and hepatotoxicity in rats. Iran J. Basic Med Sci. 2021; 24 (8): 1041–9. doi: 10.22038/ijbms.2021.55009.12331.
  33. Alexander J., Olsen A.K. Selenium – a scoping review for Nordic Nutrition Recommendations 2023. Food Nutr Res. 2023; 67. doi: 10.29219/fnr.v67.10320.
  34. Thomson C.D., Steven S.M., van Rij A.M., Wade C.R., Robinson M.F. Selenium and vitamin E supplementation: activities of glutathione peroxidase in human tissues. Am. J. Clin. Nutr. 1988; 48 (2): 316–23. doi: 10.1093/ajcn/48.2.316.
  35. Badri S., Vahdat S., Pourfarzam M., Assarzadeh S., Seirafian S., Ataei S. Potential Benefits of Selenium Supplementation in Patients with Kidney Disease. J. Res Pharm Pract. 2022; 10 (4): 149–58. doi: 10.4103/jrpp.jrpp_3_22.
  36. Zachara B.A., Adamowicz A., Trafikowska U., Trafikowska A. et al. Selenium and glutathione levels, and glutathione peroxidase activities in blood components of uremic patients on hemodialysis supplemented with selenium and treated with erythropoietin. J. Trace Elem Med Biol. 2001; 15 (4): 201–8. doi: 10.1016/S0946-672X(01)80034-1.
  37. Nève J. Human selenium supplementation as assessed by changes in blood selenium concentration and glutathione peroxidase activity. J. Trace Elem Med Biol. 1995; 9 (2): 65–73. doi: 10.1016/S0946-672X(11)80013-1.
  38. Oliveira-Silva J.A., Yamamoto J.U.P., Oliveira R.B., Monteiro V.C.L. et al. Oxidative stress assessment by glutathione peroxidase activity and glutathione levels in response to selenium supplementation in patients with Mucopolysaccharidosis I, II and VI. Genet Mol Biol. 2019; 42 (1): 1–8. doi: 10.1590/1678-4685-GMB-2017-0334.
  39. Hasani M., Djalalinia S., Khazdooz M., Asayesh H. et al. Effect of selenium supplementation on antioxidant markers: a systematic review and meta-analysis of randomized controlled trials. Hormones (Athens). 2019; 18 (4): 451–62. doi: 10.1007/s42000-019-00143-3. Epub 2019 Dec 10. Erratum in: Hormones (Athens). 2020; 19 (3): 451. doi: 10.1007/s42000-020-00224-8.
  40. Chen W., Hu F., Gao Q. et al. Tumor acidification and GSH depletion by bimetallic composite nanoparticles for enhanced chemodynamic therapy of TNBC. J. Nanobiotechnol. 2024; 22: 98. https://doi.org/10.1186/s12951-024-02308-8.
  41. Minich D.M., Brown B.I. A Review of Dietary (Phyto)Nutrients for Glutathione Support. Nutrients. 2019; 11 (9): 2073. doi: 10.3390/nu11092073. PMID: 31484368; PMCID: PMC6770193.

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2. Fig. 1. Glutathione levels and associated diseases

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3. Fig. 2. The process of hepatic GSH synthesis and interactions with nutrient substrates, cofactors, and other nutrients that affect metabolism (adapted from [41])

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