Potential use of glutathione as a treatment for Parkinson's disease

Wang,Hai-Li; Zhang,Jun; Li,Yu-Ping; Dong,Lun; Chen,Ying-Zhu

doi:10.3892/etm.2020.9557

Potential use of glutathione as a treatment for Parkinson's disease

Authors:
- Hai-Li Wang
- Jun Zhang
- Yu-Ping Li
- Lun Dong
- Ying-Zhu Chen
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Affiliations: Department of Clinical Medicine, Dalian Medical University, Dalian, Liaoning 116000, P.R. China, Department of Neurosurgery, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China, Department of Neurology, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
Published online on: December 4, 2020 https://doi.org/10.3892/etm.2020.9557
Article Number: 125
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to assess the efficacy and safety of glutathione (GSH) for the treatment of Parkinson's disease (PD). The PubMed, Cochrane Library, OvidSP, Web of Science, China Science and Technology Journal Database, Chinese National Knowledge Infrastructure and China Wanfang Standards Database databases were systematically searched from the inception dates to October 1st, 2019, using the key words‘glutathione’ or ‘GSH’ and ‘Parkinson’ or ‘Parkinson's disease’ or ‘PD’. The quality of the included articles was assessed using the bias risk assessment tool of the Cochrane systematic evaluator manual (version 5.1.0). Pooled analysis of the relevant data was performed using RevMan 5.3 software and subgroup analysis was performed to determine the impact of the dosage (300 vs. 600 mg) on the outcome measures. A total of seven randomized controlled trials involving 450 participants were included in the meta‑analysis. The results of the present study indicated a statistically significant difference between the GSH and control groups, in terms of the Unified Parkinson's Disease Rating Scale (UPDRS) III [standard mean difference (SMD), ‑0.48; 95% CI, ‑(0.88‑0.08); P=0.02] and GSH peroxidase (SMD, 1.88; 95% CI, 0.52‑3.24; P=0.007). However, the differences in the UPDRS I (SMD, ‑0.04; 95% CI, ‑0.25‑0.16; P=0.70) and UPDRS II (SMD, 0.03; 95% CI, ‑0.17‑0.24; P=0.77) score and in side effects were not statistically significant between the groups. Subgroup analyses revealed that the dosage (300 vs. 600 mg) was an influencing factor for UPDRS III. The present study demonstrated that GSH may mildly improve motor scores in PD, but not at the expense of increased adverse events.

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1	Panicker N, Kanthasamy A and Kanthasamy AG: Fyn amplifies NLRP3 inflammasome signaling in Parkinson's disease. Aging (Albany NY). 11:5871–5873. 2019.PubMed/NCBI View Article : Google Scholar
2	Grespi F and Melino G: P73 and age-related diseases: Is there any link with Parkinson disease? Aging (Albany NY). 4:923–931. 2012.PubMed/NCBI View Article : Google Scholar
3	Tamano H, Nishio R, Morioka H and Takeda A: Extracellular Zn²⁺ influx into nigral dopaminergic neurons plays a key role for pathogenesis of 6-hydroxydopamine-induced Parkinson's disease in rats. Mol Neurobiol. 56:435–443. 2019.PubMed/NCBI View Article : Google Scholar
4	Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, Holloway RG, Kieburtz K, Marshall FJ, Ravina BM, Schifitto G, Siderowf A and Tanner CM: Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology. 68:384–386. 2007.PubMed/NCBI View Article : Google Scholar
5	Smeyne M and Smeyne RJ: Glutathione metabolism and Parkinson's disease. Free Radic Biol Med. 62:13–25. 2013.PubMed/NCBI View Article : Google Scholar
6	Soukup SF, Vanhauwaert R and Verstreken P: Parkinson's disease: Convergence on synaptic homeostasis. EMBO J. 37(e98960)2018.PubMed/NCBI View Article : Google Scholar
7	Gaki GS and Papavassiliou AG: Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease. Neuromolecular Med. 16:217–230. 2014.PubMed/NCBI View Article : Google Scholar
8	Bisaglia M, Soriano ME, Arduini I, Mammi S and Bubacco L: Molecular characterization of dopamine-derived quinones reactivity toward NADH and glutathione: Implications for mitochondrial dysfunction in Parkinson disease. Biochim Biophys Acta. 1802:699–706. 2010.PubMed/NCBI View Article : Google Scholar
9	Díaz-Hung ML, Yglesias-Rivera A, Hernández-Zimbrón LF, Orozco-Suárez S, Ruiz-Fuentes JL, Díaz-García A, León-Martínez R, Blanco-Lezcano L, Pavón-Fuentes N and Lorigados-Pedre L: Transient glutathione depletion in the substantia nigra compacta is associated with neuroinflammation in rats. Neuroscience. 335:207–220. 2016.PubMed/NCBI View Article : Google Scholar
10	Hauser RA, Lyons KE, McClain T, Carter S and Perlmutter D: Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease. Mov Disord. 24:979–983. 2009.PubMed/NCBI View Article : Google Scholar
11	Mischley LK, Lau RC, Shankland EG, Wilbur TK and Padowski JM: Phase IIb study of intranasal glutathione in Parkinson's disease. J Parkinsons Dis. 7:289–299. 2017.PubMed/NCBI View Article : Google Scholar
12	Mischley LK, Leverenz JB, Lau RC, Polissar NL, Neradilek MB, Samii A and Standish LJ: A randomized, double-blind phase I/IIa study of intranasal glutathione in Parkinson's disease. Mov Disord. 30:1696–1701. 2015.PubMed/NCBI View Article : Google Scholar
13	Higgins JPT and Green S (eds): Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. urihttp://training.cochrane.org/handbooksimplehttp://training.cochrane.org/handbook.
14	Bao H: Clinical effect of reduced glutathione on Parkinson's disease. Chin J Clin Ration Drug Use. 11:44–45. 2018.(In Chinese).
15	Bao Y, Wang H, Chen H, Zhang B, Wang X, Xu G, Tong J, Wang Y and Yang X: An observation of 30 cases of Parkinson's disease treated with glutathiono. Anhui Med Pharmaceutical J. 7:22–24. 2003.(In Chinese).
16	Hu Y and Yang W: Clinical study of reduced glutathione in the treatment of Parkinsons disease. Chin J Pract Nervous Dis. 22:720–724. 2019.(In Chinese).
17	Zhang Y, Cao X, Hu H and Sun S: Therapeutic effect of reduced glutathione for Parkinson disease. Chin J Rehabil. 20:29–30. 2005.(In Chinese).
18	Aquilano K, Baldelli S and Ciriolo MR: Glutathione: New roles inredox signaling for an old antioxidant. Front Pharmacol. 5(196)2014.PubMed/NCBI View Article : Google Scholar
19	Fitzmaurice PS, Ang L, Guttman M, Rajput AH, Furukawa Y and Kish SJ: Nigral glutathione deficiency is not specific for idiopathic Parkinson's disease. Mov Disord. 18:969–976. 2003.PubMed/NCBI View Article : Google Scholar
20	Pearce RK, Owen A, Daniel S, Jenner P and Marsden CD: Alterations in the distribution of glutathione in the substantia nigra in Parkinson's disease. J Neural Transm (Vienna). 104:661–677. 1997.PubMed/NCBI View Article : Google Scholar
21	Liddell JR and White AR: Nexus between mitochondrial function, iron, copper and glutathione in Parkinson's disease. eurochem Int. 117:126–138. 2018.PubMed/NCBI View Article : Google Scholar
22	Mischley LK, Standish LJ, Weiss NS, Padowski JM, Kavanagh TJ, White CC and Rosenfeld ME: Glutathione as a biomarker in Parkinson's disease: Associations with aging and disease severity. Oxid Med Cell Longev. 2016(9409363)2016.PubMed/NCBI View Article : Google Scholar
23	Chinta SJ and Andersen JK: Reversible inhibition of mitochondrial complex I activity following chronic dopaminergic glutathione depletion in vitro: Implications for Parkinson's disease. Free Radic Biol Med. 41:1442–1448. 2006.PubMed/NCBI View Article : Google Scholar
24	Sechi G, Deeden MG, Bua G, Satta WM, Deiana GA, Pes GM and Rosati G: Reduced intraveous glutathione in the treatment of ealy Parkinson's disease. Prog Neuropsychopharmacol Biol Psychiatry. 20:1159–1170. 1996.PubMed/NCBI View Article : Google Scholar
25	Mischley LK: Glutathione deficiency in Parkinson's disease: Intranasal administration as a method of augmentation. J Orthomol Med. 26:32–36. 2011.
26	Zhou GH, Pao YC and Lu JM: The effect of glutathione on oxidation stress of Parkinson's disease rat. Chin J Behav Med Sci. 13:267–268. 2004.(In Chinese).
27	Bharath S, Hsu M, Kaur D, Rajagopalan S and Andersen JK: Glutathione,iron and Parkinson's disease. Biochem Pharmacol. 64:1037–1048. 2002.PubMed/NCBI View Article : Google Scholar
28	Klivenyi P, Andreassen OA, Ferrante RJ, Dedeoglu A, Mueller G, Lancelot E, Bogdanov M, Andersen JK, Jiang D and Beal MF: Mice deficient in cellular glutathione peroxidase show increased vulnerability to malonate, 3-nitropropionic acid, and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. J Neurosci. 20:1–7. 2000.PubMed/NCBI View Article : Google Scholar
29	Dalhoff K, Ranek L, Mantoni M and Poulsen HE: Glutathione treatment of hepatocellular carcinoma. Liver. 12:342–343. 1992.PubMed/NCBI View Article : Google Scholar
30	Tedeschi M, De Cesare A, Oriana S, Perego P, Silva A, Venturino P and Zunino F: The role of glutathione in combination with cisplatin in the treatment of ovarian cancer. Cancer Treat Rev. 18:253–259. 1991.PubMed/NCBI View Article : Google Scholar