https://doi.org/10.4081/gc.2022.10390

Glutathione: pharmacological aspects and implications for clinical use

Vol. 8 No. 2 (2022)
Submitted: 30 January 2022
Accepted: 27 September 2022
Published: 30 September 2022
Glutathione, aging, frailty.
Abstract Views: 917
PDF: 327
HTML: 601
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Andrea Novelli
Department of Health Sciences, Clinical Pharmacology and Oncology Section, University of Firenze, Italy.
Angelo Bianchetti
angelo.bianchetti.58@gmail.com
Medicine and Rehabilitation Department, Istituto Clinico S. Anna Hospital, Gruppo San Donato, Brescia, Italy; and University of Brescia, Brescia, Italy.

Glutathione is a tripeptide found in many tissues which plays a pivotal role in critical physiological processes such as maintenance of redox balance, reduction of oxidative stress by enhancement of metabolic detoxification of both xenobiotic and endogenous compounds, and regulation of immune system function. Glutathione depletion is associated with many chronic degenerative diseases and loss of function with aging and altered glutathione metabolism has been implicated in central nervous system diseases, frailty and sarcopenia, infected state, chronic liver diseases, metabolic diseases, pulmonary and cardiovascular diseases. Therefore, the glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Here we describe the main pharmacological aspects of glutathione, focusing on its synthesis and role in several vital functions including antioxidant defense, detoxification of xenobiotics and modulation of immune function and fibrogenesis and the clinical implications of its depletion and we discuss the different strategies for increasing glutathione cellular levels either by providing specific precursors and cofactors or directly administering the tripeptide.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Crossref
Scopus
Google Scholar
Europe PMC
Pizzorno J. Glutathione. Integr Med 2014;13:8-12.
Barnabeu-Wittel M, Gómez-Díaz R, González-Molina Á, et al. Oxidative stress, telomere shortening, and apoptosis associated to sarcopenia and frailty in patients with multimorbidity. J Clin Med 2020;9:2669. DOI: https://doi.org/10.3390/jcm9082669
Ballatori N, Krance SM, Notenboom S, et al. Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem 2009;390:191-214. DOI: https://doi.org/10.1515/BC.2009.033
Minich DM, Brown BI. A review of dietary (Phyto). Nutrients for glutathione support. Nutrients 2019;11:2073-93. DOI: https://doi.org/10.3390/nu11092073
Lu SC. Glutathione synthesis. Biochim Biophys Acta 2013;1830:3143-53. DOI: https://doi.org/10.1016/j.bbagen.2012.09.008
Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med 2009;30:1-12. DOI: https://doi.org/10.1016/j.mam.2008.08.006
Fawaz MV, Topper ME, Firestine SM. The ATP-grasp enzymes. Bioorg Chem 2011;39:185-219. DOI: https://doi.org/10.1016/j.bioorg.2011.08.004
Fyfe PK, Alphey MS, Hunter WN. Structure of Trypanosoma brucei glutathione synthetase: Domain and loop alterations in the catalytic cycle of a highly conserved enzyme. Mol Biochem Parasitol 2010;170:93-9. DOI: https://doi.org/10.1016/j.molbiopara.2009.12.011
Lu SC, Mato JM. S-adenosylmethionine in liver health, injury, and cancer. Physiol Rev 2012;92:1515-42. DOI: https://doi.org/10.1152/physrev.00047.2011
Yin J, Ren W, Yang G, et al. L-Cysteine metabolism and its nutritional implications. Mol Nutr Food Res 2016;60:134-46. DOI: https://doi.org/10.1002/mnfr.201500031
Wu G, Fang Y-Z, Yang S, et al. Glutathione metabolism and its implications for health. J Nutr 2004;134:489-92. DOI: https://doi.org/10.1093/jn/134.3.489
Couto N, Wood J, Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radic Biol Med 2016;95:27-42. DOI: https://doi.org/10.1016/j.freeradbiomed.2016.02.028
Lee D-H, Jacobs DR. Hormesis and public health: can glutathione depletion and mitochondrial dysfunction due to very low-dose chronic exposure to persistent organic pollutants be mitigated? J Epidemiol Community Health 2015;69:294-300. DOI: https://doi.org/10.1136/jech-2014-203861
Venditti P, DiStefano L, DiMeo S. Mitochondrial metabolism of reactive oxygen species. Mitochondrion 2013;13:71-82. DOI: https://doi.org/10.1016/j.mito.2013.01.008
Mangiapane P. Selenium and selenoproteins: an overview on different biological systems. Curr Protein Pept Sci 2014;15. DOI: https://doi.org/10.2174/1389203715666140608151134
Brigelius-Flohe R, Maiorino M. Glutathione peroxidases. Biochim Biophys Acta 2013;1830:3289-303. DOI: https://doi.org/10.1016/j.bbagen.2012.11.020
Legault J, Carrier C, Petrov P, et al. Mitochondrial GPx1 decreases induced but not basal oxidative damage to mtDNA in T47D cells. Biochem Biophys Res Commun 2000;272:416-22. DOI: https://doi.org/10.1006/bbrc.2000.2800
Mari M, Morales A, Colell A et al. Mitochondrial glutathione, a key survival antioxidant. Antioxid Redox Signal 2009;11:2685-700. DOI: https://doi.org/10.1089/ars.2009.2695
Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev 1979;59:527-605. DOI: https://doi.org/10.1152/physrev.1979.59.3.527
Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell 2012;48:158-67. DOI: https://doi.org/10.1016/j.molcel.2012.09.025
Pompella A, Visvikis A, Paolicchi A, et al. The changing faces of glutathione, a cellular protagonist. Biochem Pharmacol 2003;66:1499-503. DOI: https://doi.org/10.1016/S0006-2952(03)00504-5
Filomeni G, Aquilano K, Civitareale P, et al. Activation of c-Jun-N-terminal kinase is required for apoptosis triggered by glutathione disulfide in neuroblastoma cells. Free Radic Biol Med 2005;39:345-54. DOI: https://doi.org/10.1016/j.freeradbiomed.2005.03.022
Huang KP, Huang FL. Glutathionylation of proteins by glutathione disulfide S-oxide. Biochem Pharmacol 2002;64:1049-56. DOI: https://doi.org/10.1016/S0006-2952(02)01175-9
Olafsdottir K, Reed DJ. Retention of oxidized glutathione by isolated rat liver mitochondria during hydroperoxide treatment. Biochim Biophys Acta 1988;964:377-82. DOI: https://doi.org/10.1016/0304-4165(88)90038-4
Yin F, Sancheti H, Cadenas E. Mitochondrial thiols in the regulation of cell death pathways. Antioxid Redox Signal 2012;17:1714-27. DOI: https://doi.org/10.1089/ars.2012.4639
Aniya Y, Imaizumi N. Mitochondrial glutathione transferases involving a new function for membrane permeability transition pore regulation. Drug Metab Rev 2011;43:292-9. DOI: https://doi.org/10.3109/03602532.2011.552913
Li W, James MO, McKenzie SC, et al. Mitochondrion as a novel site of dichloroacetate biotransformation by glutathione transferase zeta1. J Pharmacol Exp Ther 2011;336:87-94. DOI: https://doi.org/10.1124/jpet.110.173195
Teixeira FK, Menezes-Benavente L, Galvão VC, Margis-Pinheiro M. Multigene families encode the major enzymes of antioxidant metabolism in Eucalyptus grandis L. Genet Mol Biol 2005;28:529-38. DOI: https://doi.org/10.1590/S1415-47572005000400007
Gould NS, Min E, Huang J, et al. Glutathione depletion accelerates cigarette smoke-induced inflammation and airspace enlargement. Toxicol Sci 2015;147:466-74. DOI: https://doi.org/10.1093/toxsci/kfv143
Lu SC. Regulation of glutathione synthesis. Mol Aspects Med 2009;30:42-59. DOI: https://doi.org/10.1016/j.mam.2008.05.005
Franklin CC, Backos DS, Mohar I, et al. Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate-cysteine ligase. Mol Aspects Med 2009;86-98. DOI: https://doi.org/10.1016/j.mam.2008.08.009
Nakamura S, Kugiyama K, Sugiyama S, et al. Polymorphism in the 5′-flanking region of human glutamate-cysteine ligase modifier subunit gene is associated with myocardial infarction. Circulation 2002;105:2968-73. DOI: https://doi.org/10.1161/01.CIR.0000019739.66514.1E
Liu RM, Gaston Pravia KA. Oxidative stress and glutathione in TGF-β-mediated fibrogenesis. Free Radic Biol Med 2010;1-15. DOI: https://doi.org/10.1016/j.freeradbiomed.2009.09.026
Akerboom TPM, Bilizer M, Sies H. The relationship of biliary GSSG efflux and intracellular GSSG content in perfused rat liver. J Biol Chem 1982;257. DOI: https://doi.org/10.1016/S0021-9258(18)34713-6
Su GL. Lipopolysaccharides in liver injury: molecular mechanisms of Kupffer cell activation. Am J Physiol Gastrointest Liver Physiol 2002;283:G256-65. DOI: https://doi.org/10.1152/ajpgi.00550.2001
Yang SQ, Lin HZ, Lane MD, et al. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci U S A 1997;94:2557-62. DOI: https://doi.org/10.1073/pnas.94.6.2557
Jaeschke H. Enhanced sinusoidal glutathione efflux during endotoxin-induced oxidant stress in vivo. Am J Physiol Gastrointest Liver Physiol 1992;263:G60-8. DOI: https://doi.org/10.1152/ajpgi.1992.263.1.G60
Payabvash S, Ghahremani MH, Goliaei A et al. Nitric oxidemodulates glutathione synthesis during endotoxemia. Free Radic Biol Med 2006;41:1817-28. DOI: https://doi.org/10.1016/j.freeradbiomed.2006.09.010
Victor VM, De La Fuente M. Immune cells redox state from mice with endotoxin-induced oxidative stress. Involvement of NF-κB. Free Radic Res 2003;37:19-27. DOI: https://doi.org/10.1080/1071576021000038522
Gould NS, Min E, Day BJ. Macropinocytosis of extracellular glutathione ameliorates tumor necrosis factor α release in activated macrophages. PLoS One 2011;6:e25704. DOI: https://doi.org/10.1371/journal.pone.0025704
Thimmulappa RK, Lee H, Rangasamy T et al. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J Clin Invest 2006;116:984-95. DOI: https://doi.org/10.1172/JCI25790
Morris D, Khurasany M, Nguyen T, et al. Glutathione and infection. Biochim Biophys Acta (1830) 2013;3329-49. DOI: https://doi.org/10.1016/j.bbagen.2012.10.012
Hassan MQ, Hadi RA, Al-Rawi ZS, et al. The glutathione defense system in the pathogenesis of rheumatoid arthritis. J Appl Toxicol 2001;21:69-73. DOI: https://doi.org/10.1002/jat.736
Perl A, Gergely P Jr, Nagy G, et al. Mitochondrial hyperpolarization: a checkpoint of Tcell life, death and autoimmunity. Trends Immunol 2004;25:360-7. DOI: https://doi.org/10.1016/j.it.2004.05.001
Sido B, Hack V, Hochlehnert A, et al. Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease. Gut 1998;42:485-92. DOI: https://doi.org/10.1136/gut.42.4.485
Zargari M, Allameh A, Sanati MH, et al. Relationship between the clinical scoring and demyelination in central nervous system with total antioxidant capacity of plasma during experimental autoimmune encephalomyelitis development in mice. Neurosci Lett 2007;412:24-8. DOI: https://doi.org/10.1016/j.neulet.2006.08.033
Kokcam I, Naziroglu M. Antioxidants and lipid peroxidation status in the blood of patients with psoriasis. Clin Chim Acta 1999;289:23-31. DOI: https://doi.org/10.1016/S0009-8981(99)00150-3
Eisen M, Kaur S, Rehema A, et al. Allergic contact dermatitis is accompanied by severe abnormal changes in antioxidativity of blood. Biomed Pharmacother 2004;58:260-63. DOI: https://doi.org/10.1016/j.biopha.2004.02.005
Knight JA. The biochemistry of aging. Adv Clin Chem 2000;35:1-62. DOI: https://doi.org/10.1016/S0065-2423(01)35014-X
Viveros MP, Arranz L, Hernanz A, et al. A model of premature aging in mice based on altered stress-related behavioral response and immunosenescence. Neuroimmunomodulation 2007;14:157-62. DOI: https://doi.org/10.1159/000110640
Lang CA, Mills BJ, Mastropaolo W, Liu MC. Blood glutathione decreases in chronic diseases. J Lab Clin Med 2000;135:402-5. DOI: https://doi.org/10.1067/mlc.2000.105977
Isomura H, Fujie K, Shibata K, et al. Bone metabolism and oxidative stress in postmenopausal rats with iron overload. Toxicology 2004;197:93-100. DOI: https://doi.org/10.1016/j.tox.2003.12.006
Sanchez-Rodriguez MA, Ruiz-Ramos M, Correa-Munoz E, Mendoza-Nunez VM. Oxidative stress as a risk factor for osteoporosis in elderly mexicans as characterized by antioxidant enzymes. BMC Musculoskelet Disord 2007;8:124. DOI: https://doi.org/10.1186/1471-2474-8-124
Borrás C, Esteve JM, Viña JR, et al. Glutathione regulates telomerase activity in 3T3 fibroblasts. J Biol Chem 2004;279:34332-5. DOI: https://doi.org/10.1074/jbc.M402425200
Wei YH, Ma YS, Lee HC, et al. Mitochondrial theory of aging matures--roles of mtDNA mutation and oxidative stress in human aging. Zhonghua Yi Xue Za Zhi (Taipei) 2001;64:259-70.
Martínez de Toda I, Vida C, Garrido A, De la Fuente M. Redox parameters as markers of the rate of aging and predictors of life span. J Gerontol A Biol Sci Med Sci 2020;75:613-20. DOI: https://doi.org/10.1093/gerona/glz033
Pérez LM, Hooshmand B, Mangialasche F, et al. Glutathione serum levels and rate of multimorbidity development in older adults. J Gerontol A Biol Sci Med Sci 2020;75:1089-94. DOI: https://doi.org/10.1093/gerona/glz101
Marengoni A, Angleman S, Melis R, et al. Aging with multimorbidity: a systematic review of the literature. Ageing Res Rev 2011;10:430-9. DOI: https://doi.org/10.1016/j.arr.2011.03.003
Fabbri E, An Y, Zoli M, et al. Aging and the burden of multimorbidity: associations with inflammatory and anabolic hormonal biomarkers. J Gerontol A Biol Sci Med Sci 2015;70:63-70. DOI: https://doi.org/10.1093/gerona/glu127
Cesari M, Landi F, Vellas B, et al. Sarcopenia and physical frailty: two sides of the same coin. Front Aging Neurosci 2014;6:192. DOI: https://doi.org/10.3389/fnagi.2014.00192
Bianchetti A, Novelli A. Sarcopenia in the elderly: from clinical aspects to therapeutic options. Geriatric Care 2019;5:1. DOI: https://doi.org/10.4081/gc.2019.8033
Bernabeu-Wittel M, González-Molina Á, Fernández-Ojeda R, et al. Impact of sarcopenia and frailty in a multicenter cohort of polypathological patients. J Clin Med 2019;8:535. DOI: https://doi.org/10.3390/jcm8040535
El Assar M, Angulo J, Rodríguez-Mañas L. Frailty as a phenotypic manifestation of underlying oxidative stress. Free Radic Biol Med 2020;149:72-7. DOI: https://doi.org/10.1016/j.freeradbiomed.2019.08.011
Homma T, Fujii J. Application of glutathione as anti-oxidative and anti-aging drugs. Curr Drug Metab 2015;16:560-71. DOI: https://doi.org/10.2174/1389200216666151015114515
Gu F, Chauhan V, Chauhan A. Glutathione redox imbalance in brain disorders. Curr Opin Clin Nutr Metab Care 2015;18:89-95. DOI: https://doi.org/10.1097/MCO.0000000000000134
Dringen R. Metabolism and functions of glutathione in brain. Prog Neurobiol 2000;62:649-71. DOI: https://doi.org/10.1016/S0301-0082(99)00060-X
Lee KH, Cha M, Lee BH. Neuroprotective effect of antioxidants in the brain. Int J Mol Sci 2020;21:7152. DOI: https://doi.org/10.3390/ijms21197152
Wang W, Zhao F, Ma X, et al. Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances. Mol Neurodegeneration 2020;15:30. DOI: https://doi.org/10.1186/s13024-020-00376-6
Wojsiat J, Zoltowsk KM, Laskowska-Kaszub K, Wojda U. Oxidant/antioxidant imbalance in Alzheimer’s disease: therapeutic and diagnostic prospects. Oxid Med Cell Longev 2018;2018:6435861. DOI: https://doi.org/10.1155/2018/6435861
Shukla D, Mandal PK, Tripathi M, et al. Quantitation of in vivo brain glutathione conformers in cingulate cortex among age-matched control, MCI, and AD patients using MEGA-PRESS. Hum Brain Mapp 2020;41:194-217. DOI: https://doi.org/10.1002/hbm.24799
Dwivedi D, Megha K, Mishra R, Mandal PK. Glutathione in brain: overview of its conformations, functions, biochemical characteristics, quantitation and potential therapeutic role in brain disorders. Neurochem Res 2020;45:1461-80. DOI: https://doi.org/10.1007/s11064-020-03030-1
Liu Y, Chen Z, Li B, et al. Supplementation with γ-glutamylcysteine (γ-GC. lessens oxidative stress, brain inflammation and amyloid pathology and improves spatial memory in a murine model of AD. Neurochem Int 2021;144:104931. DOI: https://doi.org/10.1016/j.neuint.2020.104931
Smeyne M, Smeyne RJ. Glutathione metabolism and Parkinson’s disease. Free Radic Biol Med 2013;62:13-25. DOI: https://doi.org/10.1016/j.freeradbiomed.2013.05.001
Percário S, da Silva Barbosa A, Varela ELP, et al. Oxidative stress in Parkinson’s disease: potential benefits of antioxidant supplementation. Oxid Med Cell Longev 2020;2020:2360872. DOI: https://doi.org/10.1155/2020/2360872
Wang H, Zhang J, Li Y, et al. Potential use of glutathione as a treatment for Parkinson’s disease. Exp Ther Med 2021;21:125. DOI: https://doi.org/10.3892/etm.2020.9557
Fraternale A, Zara C, De Angelis M, et al. Intracellular redox-modulated pathways as targets for effective approaches in the treatment of viral infection. Int J Mol Sci 2021;22:3603. DOI: https://doi.org/10.3390/ijms22073603
Rashida Gnanaprakasam JN, Wu R, Wang R. Metabolic reprogramming in modulating T cell reactive oxygen species generation and antioxidant capacity. Front Immunol 2018;9:1075. DOI: https://doi.org/10.3389/fimmu.2018.01075
Guloyan V, Oganesian B, Baghdasaryan N, et al. Glutathione supplementation as an adjunctive therapy in COVID-19. Antioxidants (Basel) 2020;9:914. DOI: https://doi.org/10.3390/antiox9100914
Polonikov A. Endogenous deficiency of glutathione as the most likely cause of serious manifestations and death in COVID-19 patients. ACS Infect Dis 2020;6:1558-62. DOI: https://doi.org/10.1021/acsinfecdis.0c00288
Chavarría AP, Vázquez R, Cherit J, et al. Antioxidants and pentoxifylline as coadjuvant measures to standard therapy to improve prognosis of patients with pneumonia by COVID-19. Comput Struct Biotechnol J 2021;19:1379-2139. DOI: https://doi.org/10.1016/j.csbj.2021.02.009
Tosukhowong P, Boonla C, Dissayabutra T, et al. Biochemical and clinical effects of Whey protein supplementation in Parkinson’s disease: a pilot study. J Neurol Sci 2016;367:162-70. DOI: https://doi.org/10.1016/j.jns.2016.05.056
Bumrungpert A, Pavadhgul P, Nunthanawanich P, et al. Whey protein supplementation improves nutritional status, glutathione levels, and immune function in cancer patients: a randomized, double-blind controlled trial. J Med Food 2018;21:612-6. DOI: https://doi.org/10.1089/jmf.2017.4080
Zhou X, He L, Wu C, et al. Serine alleviates oxidative stress via supporting glutathione synthesis and methionine cycle in mice. Mol Nutr Food Res 2017;61. DOI: https://doi.org/10.1002/mnfr.201700262
Zhou X, He L, Zuo S, et al. Serine prevented high-fat diet-induced oxidative stress by activating AMPK and epigenetically modulating the expression of glutathione synthesis-related genes. Biochim Biophys Acta Mol Basis Dis 2018;1864:488-98. DOI: https://doi.org/10.1016/j.bbadis.2017.11.009
Duffy SL, Lagopoulos J, Cockayne N, 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;31:1247-54. DOI: https://doi.org/10.1016/j.nut.2015.04.019
Taghizadeh M, Tamtaji OR, Dadgostar E, et al. The effects of omega-3 fatty acids and vitamin E co-supplementation on clinical and metabolic status in patients with Parkinson’s disease: A randomized, double-blind, placebo-controlled trial. Neurochem Int 2017;108:183-9. DOI: https://doi.org/10.1016/j.neuint.2017.03.014
Gago-Dominguez M, Castelao JE, Sun C-L, et al. Marine n-3 fatty acid intake, glutathione S-transferase polymorphisms and breast cancer risk in post-menopausal Chinese women in Singapore. Carcinogenesis 2014;25:2143-7. DOI: https://doi.org/10.1093/carcin/bgh230
Sepidarkish M, Akbari-Fakhrabadi M, Daneshzad E, et al. Effect of omega-3 fatty acid plus vitamin E Co-Supplementation on oxidative stress parameters: a systematic review and meta-analysis. Clin Nutr 2020;39:1019-25. DOI: https://doi.org/10.1016/j.clnu.2019.05.004
Skvarc DR, Dean OM, Byrne LK, et al. The effect of N-acetylcysteine (NAC). on human cognition - A systematic review. Neurosci Biobehav Rev 2017;78:44-56. DOI: https://doi.org/10.1016/j.neubiorev.2017.04.013
Holmay MJ, Terpstra M, Coles LD, et al. N-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases. Clin Neuropharmacol 2013;36:103-6. DOI: https://doi.org/10.1097/WNF.0b013e31829ae713
Jannatifar R, Parivar K, Roodbari NH, Nasr-Esfahani MH. Effects of N-acetyl-cysteine supplementation on sperm quality, chromatin integrity and level of oxidative stress in infertile men. Reprod Biol Endocrinol 2019;17:24. DOI: https://doi.org/10.1186/s12958-019-0468-9
Zhang Q, Ju Y, Ma Y, Wang T. N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia: a randomized controlled trial. Medicine 2018;97:e13087. DOI: https://doi.org/10.1097/MD.0000000000013087
Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther 2014;141:150-9. DOI: https://doi.org/10.1016/j.pharmthera.2013.09.006
Ellegaard PK, Licht RW, Nielsen RE et al. The efficacy of adjunctive N-acetylcysteine in acute bipolar depression: a randomized placebo-controlled study. J Affect Disord 2019;245:1043-51. DOI: https://doi.org/10.1016/j.jad.2018.10.083
Berk M, Turner A, Malhi GS, et al. A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo. BMC Med 2019;17:18. DOI: https://doi.org/10.1186/s12916-019-1257-1
Panizzutti B, Bortolasci C, Hasebe K, et al. Mediator effects of parameters of inflammation and neurogenesis from a N-acetyl cysteine clinical-trial for bipolar depression. Acta Neuropsychiatr 2018;30:334-41. DOI: https://doi.org/10.1017/neu.2018.13
Sechi G, Deledda MG, Bua G, et al. Reduced intravenous glutathione in the treatment of early Parkinson’s disease. Prog Neuropsychopharmacol Biol Psychiatry 1996;20:1159-70. DOI: https://doi.org/10.1016/S0278-5846(96)00103-0
Otto M, Magerus T, Langland JO. The use of intravenous glutathione for symptom management of Parkinson’s disease: a case report. Altern Ther Health Med 2018;24:56-60.
Anderson ME, Meister A. Glutathione monoesters. Anal Biochem 1989;183:16-20. DOI: https://doi.org/10.1016/0003-2697(89)90164-4
Richie JP Jr, Nichenametla S, Neidig,W et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr 2015;54:251-63. DOI: https://doi.org/10.1007/s00394-014-0706-z
Sinha R, Sinha I, Calcagnotto A, et al. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Eur J Clin Nutr 2018; 72:105-11. DOI: https://doi.org/10.1038/ejcn.2017.132
Campolo J, Bernardi S, Cozzi L, et al. Medium-term effect of sublingual glutathione supplementation on flow-mediated dilation in subjects with cardiovascular risk factors. Nutrition 2017;38:41-7. DOI: https://doi.org/10.1016/j.nut.2016.12.018
Schmitt B, Vicenzi M, Garrel C, Denis FM. Effects of N-acetylcysteine, oral glutathione (GSH. and a novel sublingual form of GSH on oxidative stress markers: a comparative crossover study. Redox Biol 2015;6:198-205. DOI: https://doi.org/10.1016/j.redox.2015.07.012
Buonocore D, Grosini M, Giardina S, et al. Bioavailability study of an innovative orobuccal formulation of glutathione. Oxid Med Cell Longev 2016. DOI: https://doi.org/10.1155/2016/3286365
Kantah MK, Kumari A, He F, et al. An orally-bioavailable glutathione-based hepatoprotective compound in experimental acute liver injury: more effective than silymarin and YHK. J Gastrointest Dig Syst 2016;6:462. DOI: https://doi.org/10.4172/2161-069X.1000462
Makida Y, He F, Mohania D, et al. Effect of a novel GSH-based compound and chabasite-phillipsite-based chelator in environmentally exposed poor detoxifiers: an adjuvant hepatoprotective treatment for poly-drug users? Metabolomics (Los Angel) 2016;6:185. DOI: https://doi.org/10.4172/2153-0769.1000185

How to Cite

Novelli, A., & Bianchetti, A. (2022). Glutathione: pharmacological aspects and implications for clinical use. Geriatric Care, 8(2). https://doi.org/10.4081/gc.2022.10390

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.