Pramipexole Enhances Levodopa's Therapeutic Efficacy in Parkinson’s Disease: role of glutaredoxin-1 (Grx1), peroxiredoxin-3 (Prx3), thioredoxin (Trx), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and neurosteroid dehydroepiandrosterone sulfate (DHEA-S)

  • Yu Shu Department of Neurology, The Fourth People's Hospital of Zhenjiang, Zhenjiang, Jiangsu 212000, China.
  • Jinjun Qian Department of Neurology, The Fourth People's Hospital of Zhenjiang, Zhenjiang, Jiangsu 212000, China.
DOI: https://doi.org/10.5937/jomb0-59700
Keywords: Parkinson's disease, Levodopa, Pramipexole, Oxidative stress, Glutaredoxin-1, Peroxiredoxin-3, Thioredoxin, 8-OHdG, UPDRS, MMSE, MOCA, Cognition, Motor function, Neurosteroids

Abstract


Background: Parkinson's disease (PD) is characterized by progressive neurodegeneration and dopamine deficiency. Levodopa remains a cornerstone treatment, but its long-term use is associated with motor complications and reduced efficacy. This study investigates the clinical benefits of combining pramipexole with levodopa in PD patients, focusing on improvements in oxidative stress, cognitive function, and motor control. Additionally, the study explores the role of novel biomarkers, including glutaredoxin-1 (Grx1), peroxiredoxin-3 (Prx3), thioredoxin (Trx), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and neurosteroid dehydroepiandrosterone sulfate (DHEA-S), in evaluating oxidative stress and neuroprotection.

Methods: A total of 92 PD patients were enrolled and assigned to either a levodopa monotherapy group (n=46) or a pramipexole-levodopa combination group (n=46). Clinical efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS). Cognitive function was evaluated using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Oxidative stress markers (SOD, GSH, GSH-PX, CAT, along with Grx1, Prx3, Trx, and 8-OHdG) were measured in serum samples. Additionally, DHEA-S was analyzed as a neurosteroid biomarker to assess its potential role in cognitive and motor function improvements. Quality of life (QOL) was assessed using the PDQ-39 questionnaire.

Results: The combination therapy group exhibited a significantly higher effective rate (93.48%) compared to the levodopa group (78.26%) (P < 0.05). UPDRS scores were significantly lower in the combination group at 6 and 12 weeks post-treatment (P < 0.05). The combination group also showed a significantly lower incidence of adverse drug reactions (6.52% vs. 23.91%, P < 0.05). After 3 months, the combination group displayed significantly higher levels of SOD, GSH, GSH-PX, CAT, Grx1, Prx3, and Trx, while 8-OHdG levels were significantly reduced, indicating enhanced neuroprotection and reduced oxidative stress. DHEA-S levels were also elevated, correlating with improved MMSE and MoCA scores (P < 0.05), suggesting a neurosteroid-mediated cognitive benefit. QOL was significantly better in the combination group after 3 months of intervention (P < 0.05).

Conclusions: Pramipexole combined with levodopa significantly improves clinical outcomes, reduces adverse effects, enhances cognitive function, and alleviates oxidative stress in PD patients. The inclusion of novel biomarkers such as Grx1, Prx3, Trx, 8-OHdG, and DHEA-S provides deeper insight into the molecular mechanisms underlying these therapeutic effects. This combination therapy represents a valuable strategy for improving PD management and warrants wider clinical application.

 

References

1. Postuma RB, Gagnon JF, Bertrand JA, Génier Marchand D, Montplaisir JY. Parkinson risk in idiopathic REM sleep behavior disorder: preparing for neuroprotective trials. Neurology. 2015;84(11):1104-13.
2. Ramezani SR, Mojra A, Tafazzoli-Shadpour M. Investigating the effects of substrate stiffness on half-maximal inhibitory concentration of chemical anticancer drugs, cell viability and migration of cell lines. Cell Mol Biomed Rep. 2025;5(3):141-7.
3. Reddy KTK, Reddy AS. Recent Breakthroughs in Drug Delivery Systems for Targeted Cancer Therapy: An Overview. Cell Mol Biomed Rep. 2025;5(1):13-27.
4. Hauser RA, Pahwa R, Tanner CM, Oertel W, Isaacson SH, Johnson R, et al. ADS-5102 (Amantadine) Extended-Release Capsules for Levodopa-Induced Dyskinesia in Parkinson's Disease (EASE LID 2 Study): Interim Results of an Open-Label Safety Study. J Parkinsons Dis. 2017;7(3):511-22.
5. Paspula PM, Naaz S, Moukthika E, Shazaa S, Bhuvaneshwari P, Sultana S, et al. A study evaluating the risk factors and different treatment modalities for osteoporosis. Cell Mol Biomed Rep. 2025;5(1):39-47.
6. Elgueta D, Aymerich MS, Contreras F, Montoya A, Celorrio M, Rojo-Bustamante E, et al. Pharmacologic antagonism of dopamine receptor D3 attenuates neurodegeneration and motor impairment in a mouse model of Parkinson's disease. Neuropharmacology. 2017;113(Pt A):110-23.
7. Antonini A, Calandrella D. Once-daily pramipexole for the treatment of early and advanced idiopathic Parkinson's disease: implications for patients. Neuropsychiatr Dis Treat. 2011;7:297-302.
8. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015;30(12):1591-601.
9. Pahwa R, Tanner CM, Hauser RA, Sethi K, Isaacson S, Truong D, et al. Amantadine extended release for levodopa-induced dyskinesia in Parkinson's disease (EASED Study). Mov Disord. 2015;30(6):788-95.
10. Zhang J, Tan LC. Revisiting the Medical Management of Parkinson's Disease: Levodopa versus Dopamine Agonist. Curr Neuropharmacol. 2016;14(4):356-63.
11. Xiang W, Sun YQ, Teoh HC. Comparison of nocturnal symptoms in advanced Parkinson's disease patients with sleep disturbances: pramipexole sustained release versus immediate release formulations. Drug Des Devel Ther. 2018;12:2017-24.
12. Wang Y, Sun SG, Zhu SQ, Liu CF, Liu YM, Di Q, et al. Analysis of pramipexole dose-response relationships in Parkinson's disease. Drug Des Devel Ther. 2017;11:83-9.
13. Smith JA, Das A, Ray SK, Banik NL. Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Res Bull. 2012;87(1):10-20.
14. Wang Q, Liu Y, Zhou J. Neuroinflammation in Parkinson's disease and its potential as therapeutic target. Transl Neurodegener. 2015;4:19.
15. Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, et al. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008;23(15):2129-70.
16. Skorga P, Young CF. Mini-Mental State Examination for the Detection of Alzheimer Disease and Other Dementias in People With Mild Cognitive Impairment. Clin Nurse Spec. 2015;29(5):265-7.
17. Lindholm D, Mäkelä J, Di Liberto V, Mudò G, Belluardo N, Eriksson O, et al. Current disease modifying approaches to treat Parkinson's disease. Cell Mol Life Sci. 2016;73(7):1365-79.
18. Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. Jama. 2014;311(16):1670-83.
19. Poewe W, Antonini A, Zijlmans JC, Burkhard PR, Vingerhoets F. Levodopa in the treatment of Parkinson's disease: an old drug still going strong. Clin Interv Aging. 2010;5:229-38.
20. Politis M, Wu K, Loane C, Brooks DJ, Kiferle L, Turkheimer FE, et al. Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson's disease patients. J Clin Invest. 2014;124(3):1340-9.
21. LeWitt PA. Levodopa therapy for Parkinson's disease: Pharmacokinetics and pharmacodynamics. Mov Disord. 2015;30(1):64-72.
22. Felger JC, Hernandez CR, Miller AH. Levodopa reverses cytokine-induced reductions in striatal dopamine release. Int J Neuropsychopharmacol. 2015;18(4).
23. Faddoul L, Chahine B, Haydar S, Abourida S, Hallit S, Raad EB. The effect of pramipexole extended release on the levodopa equivalent daily dose in Lebanese Parkinson diseased patients. Pharm Pract (Granada). 2018;16(4):1220.
24. Foster PS, Yung RC, Drago V, Crucian GP, Heilman KM. Working memory in Parkinson's disease: the effects of depression and side of onset of motor symptoms. Neuropsychology. 2013;27(3):303-13.
Published
2025/08/27
Issue
Ahead of print
Section
Original paper

Copyright (c) 2025 Yu Shu, Jinjun Qian

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