1. Russian Center for Neurology and Neurosciences, Moscow, Russia 2. Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia 3. Scientific Research Institute of Systems Biology and Medicine, Moscow, Russia 4. Institute of Biomedical Chemistry, Moscow, Russia 5. The World-class Center for Genomic Research “Center for Predictive Genetics, Pharmacogenetics and Personalized Therapy” of the Academician B.V. Petrovsky, Russian Scientific Center of Surgery, Moscow, Russia; Russian Medical Academy of Continuing Professional Education, Moscow, Russia
The blood serum antioxidant status and the blood plasma metabolomic profile have been analyzed in Parkinson's disease (PD) patients, both pharmacologically naive and taking levodopa (treatment duration 7.4±5.4 years) at low (< 300 mg/day) and high (> 300 mg/day) doses. High-dose levodopa therapy caused changes in both the antioxidant status and metabolome of patients. High-dose levodopa treatment also activated lipid peroxidation, manifested by an increase in the level of lipid hydroperoxides. High-resolution mass spectrometry revealed accumulation of levodopa and dopamine metabolic products in the metabolome, particularly the neurotoxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), and associated changes in related metabolic pathways. Low-dose levodopa treatment did not cause significant changes in the antioxidant status and metabolome of patients, thus suggesting that maintaining a low-dose regimen as long as possible could potentially reduce neurotoxic metabolite accumulation and also maintain normal antioxidant functions in PD patients.
Download PDF:
Keywords: levodopa, Parkinson`s disease, metabolome, pharmacometabolomics, dopamine, mass spectrometry
Citation:
Abaimov D.A., Fedorova T.N., Shabalina A.A., Silantyev A.S., Konanov D.N., Fedotova E.Yu., Poleshchuk V.V., Andreev M.N., Trifonova O.V., Maslov D.L., Balashova E.E., Sychev D.A., Illarioshkin S.N., Lokhov P.G. (2026) The effect of levodopa on the blood antioxidant system and metabolome in patients with Parkinson's disease. Biomeditsinskaya Khimiya, 72(2), 141-151.
Abaimov D.A. et al. The effect of levodopa on the blood antioxidant system and metabolome in patients with Parkinson's disease // Biomeditsinskaya Khimiya. - 2026. - V. 72. -N 2. - P. 141-151.
Abaimov D.A. et al., "The effect of levodopa on the blood antioxidant system and metabolome in patients with Parkinson's disease." Biomeditsinskaya Khimiya 72.2 (2026): 141-151.
Abaimov, D. A., Fedorova, T. N., Shabalina, A. A., Silantyev, A. S., Konanov, D. N., Fedotova, E. Yu., Poleshchuk, V. V., Andreev, M. N., Trifonova, O. V., Maslov, D. L., Balashova, E. E., Sychev, D. A., Illarioshkin, S. N., Lokhov, P. G. (2026). The effect of levodopa on the blood antioxidant system and metabolome in patients with Parkinson's disease. Biomeditsinskaya Khimiya, 72(2), 141-151.
References
Whitfield A.C., Moore B.T., Daniels R.N. (2014) Classics in chemical neuroscience: levodopa. ACS Chem. Neurosci., 5(12), 1192–1197. CrossRef Scholar google search
Mena M.A., Casarejos M.J., Solano R.M., de Yébenes J.G. (2009) Half a century of L-DOPA. Curr. Top. Med. Chem., 9(10), 880–893. CrossRef Scholar google search
Chagraoui A., Boulain M., Juvin L., Anouar Y., Barrière G., de Deurwaerdère P. (2020) L-DOPA in Parkinson’s disease: looking at the “false” neurotransmitters and their meaning. Int. J. Mol. Sci., 21(1), 294. CrossRef Scholar google search
Müller T. (2013) Detoxification and antioxidative therapy for levodopa-induced neurodegeneration in Parkinson’s disease. Expert Rev. Neurother., 13(6), 707–718. CrossRef Scholar google search
Olanow C.W. (2015) Levodopa: effect on cell death and the natural history of Parkinson's disease. Mov. Disord., 30(1), 37–44. CrossRef Scholar google search
Paul R., Borah A. (2016) L-DOPA-induced hyperhomocysteinemia in Parkinson's disease: elephant in the room. Biochim. Biophys. Acta, 1860(9), 1989–1997. CrossRef Scholar google search
Melamed E., Offen D., Shirvan A., Ziv I. (2000) Levodopa — an exotoxin or a therapeutic drug? J. Neurol., 247(Suppl 2), 135–139. CrossRef Scholar google search
Jenner P. (2015) Treatment of the later stages of Parkinson’s disease — pharmacological approaches now and in the future. Transl. Neurodegener., 4, 3. CrossRef Scholar google search
Götz M.E., Double K., Gerlach M., Youdim M.B.H., Riederer P. (2004) The relevance of iron in the pathogenesis of Parkinson's disease. Ann. NY Acad. Sci., 1012, 193–208. CrossRef Scholar google search
Serra J.A., Domínguez R.O., de Lustig E.S., Guareschi E.M., Famulari A.L., Bartolomé E.L., Marschoff E.R. (2001) Parkinson's disease is associated with oxidative stress: comparison of peripheral antioxidant profiles in living Parkinson's, Alzheimer's and vascular dementia patients. J. Neural Transm. (Vienna), 108(10), 1135–1148. CrossRef Scholar google search
Duran R., Barrero F.J., Morales B., Luna J.D., Ramirez M., Vives F. (2011) Oxidative stress and aminopeptidases in Parkinson’s disease patients with and without treatment. Neurodegener. Dis., 8(3), 109–116. CrossRef Scholar google search
Gonzalez-Covarrubias V., Martínez-Martínez E., del Bosque-Plata L. (2022) The potential of metabolomics in biomedical applications. Metabolites, 12(2), 194. CrossRef Scholar google search
Shao Y., Li T., Liu Z., Wang X., Xu X., Li S., Xu G., Le W. (2021) Comprehensive metabolic profiling of Parkinson’s disease by liquid chromatography-mass spectrometry. Mol. Neurodegener., 16, 4. CrossRef Scholar google search
Branco R.C., Ellsworth W., Niedzwiecki M.M., Butkovich L.M., Walker D.I., Huddleston D.E., Jones D.P., Miller G.W. (2018) Levodopa and dopamine dynamics in Parkinson’s disease metabolomics. BioRxiv, 306266. CrossRef Scholar google search
Rodriguez-Violante M., Cervantes-Arriaga A. (2014) The movement disorder society-unified Parkinson’s disease rating scale: clinical and research uses. Archivos de Neurociencias, 19(3), 157–163. CrossRef Scholar google search
Vladimirov Y.A. (1996) Studies of the antioxidant activity by measuring chemiluminescence kinetics. In: Proceedings of the International Symposium on Natural Antioxidants: Molecular Mechanisms and Health Effects (Packer L., Traber M.G., Xin W., eds.), AOCS Press, Champaign, Il., pp. 125–144. Scholar google search
Fedorova T.N. (2003) Chemiluminescent analysis used for the comparative assessment of the antioxidant activity of pharmacological compounds. Eksperimentalnaya i Klinicheskaya Farmakologiya, 66(5), 56–58. CrossRef Scholar google search
Fedorova T.N., Devyatov A.A., Berezhnoi D.S., Stvolinskii S.L., Morozova M.P., Gavrilova S.A., Tutelyan V.A. (2018) Oxidative status in different areas of the cerebral cortex of Wistar rats during focal ischemia and its modulation with carnosine. Bull. Exp. Biol. Med., 165(6), 746–750. CrossRef Scholar google search
Lokhov P.G., Balashova E.E., Voskresenskaya A.A., Trifonova O.P., Maslov D.L., Archakov A.I. (2016) Mass spectrometric signatures of the blood plasma metabolome for disease diagnostics. Biomed. Rep., 4(1), 122–126. CrossRef Scholar google search
Lokhov P.G., Dashtiev M.I., Moshkovskii S.A., Archakov A.I. (2010) Metabolite profiling of blood plasma of patients with prostate cancer. Metabolomics, 6(1), 156–163. CrossRef Scholar google search
Wishart D.S., Tzur D., Knox C., Eisner R., Guo A.C., Young N., Cheng D., Jewell K., Arndt D., Sawhney S., Fung C., Nikolai L., Lewis M., Coutouly M.A., Forsythe I., Tang P., Shrivastava S., Jeroncic K., Stothard P., Amegbey G., Block D., Hau D.D., Wagner J., Miniaci J., Clements M., Gebremedhin M., Guo N., Zhang Y., Duggan G.E., Macinnis G.D., Weljie A.M., Dowlatabadi R., Bamforth F., Clive D., Greiner R., Li L., Marrie T., Sykes B.D., Vogel H.J., Querengesser L. (2007) HMDB: the Human Metabolome Database. Nucleic Acids Res., 35(Database issue), D521–D526. CrossRef Scholar google search
Nyangale E.P., Mottram D.S., Gibson G.R. (2012) Gut microbial activity, implications for health and disease: the potential role of metabolite analysis. J. Proteome Res., 11(12), 5573–5585. CrossRef Scholar google search
Heetun Z.S., Quigley E.M.M. (2012) Gastroparesis and Parkinson's disease: a systematic review. Parkinsonism Relat. Disord., 18(5), 433–440. CrossRef Scholar google search
Kori M., Aydın B., Unal S., Arga K.Y., Kazan D. (2016) Metabolic biomarkers and neurodegeneration: a pathway enrichment analysis of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. OMICS, 20(11), 645–661. CrossRef Scholar google search
Contin M., Martinelli P. (2010) Pharmacokinetics of levodopa. J. Neurol., 257(Suppl 2), S253–S261. CrossRef Scholar google search
Goldstein D.S. (2021) The catecholaldehyde hypothesis for the pathogenesis of catecholaminergic neurodegeneration: what we know and what we do not know. Int. J. Mol. Sci., 22(11), 5999. CrossRef Scholar google search
Marchitti S.A., Deitrich R.A., Vasiliou V. (2007) Neurotoxicity and metabolism of the catecholamine-derived 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde: the role of aldehyde dehydrogenase. Pharmacol. Rev., 59(2), 125–150. CrossRef Scholar google search
