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No increased chromosomal damage in L-DOPA-treated patients with Parkinson's disease: a pilot study


Oli, R G; Fazeli, G; Kuhn, W; Walitza, S; Gerlach, M; Stopper, H (2010). No increased chromosomal damage in L-DOPA-treated patients with Parkinson's disease: a pilot study. Journal of Neural Transmission, 117(6):737-746.

Abstract

Parkinson's disease (PD) is a neurodegenerative movement disorder affecting about 2% of the human population in old age. L-3,4-Dihydroxyphenylalanine (L-DOPA) in combination with a peripheral aromatic amino acid decarboxylase inhibition has been the most frequently prescribed drug for alleviating symptoms of PD, but a potential contribution of L-DOPA therapy to further neurodegeneration via oxidative stress is still debated. We report that the specific oxidative stress biomarker 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) level in peripheral blood lymphocyte DNA was elevated to 8.1 +/- 1.7 8-oxodG/10(6)dG in 17 chronically L-DOPA-treated PD patients, compared to 4.6 +/- 1.2 8-oxodG/10(6)dG in 12 controls. However, the total antioxidative capacity of plasma was increased to 1113 +/- 237 microM in the PD patients compared to 941 +/- 254 microM in controls. The frequency of micronuclei, a subgroup of chromosomal aberrations, in peripheral blood lymphocytes was not elevated compared to healthy age-matched individuals. In vitro, in a cell-free assay, dopamine and its precursor L-DOPA exhibited antioxidative capacity. On the other hand, the 8-oxodG concentration in cultured PC 12 cells was enhanced after dopamine treatment. This elevation may be below a threshold for manifestation as chromosomal damage.

Parkinson's disease (PD) is a neurodegenerative movement disorder affecting about 2% of the human population in old age. L-3,4-Dihydroxyphenylalanine (L-DOPA) in combination with a peripheral aromatic amino acid decarboxylase inhibition has been the most frequently prescribed drug for alleviating symptoms of PD, but a potential contribution of L-DOPA therapy to further neurodegeneration via oxidative stress is still debated. We report that the specific oxidative stress biomarker 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) level in peripheral blood lymphocyte DNA was elevated to 8.1 +/- 1.7 8-oxodG/10(6)dG in 17 chronically L-DOPA-treated PD patients, compared to 4.6 +/- 1.2 8-oxodG/10(6)dG in 12 controls. However, the total antioxidative capacity of plasma was increased to 1113 +/- 237 microM in the PD patients compared to 941 +/- 254 microM in controls. The frequency of micronuclei, a subgroup of chromosomal aberrations, in peripheral blood lymphocytes was not elevated compared to healthy age-matched individuals. In vitro, in a cell-free assay, dopamine and its precursor L-DOPA exhibited antioxidative capacity. On the other hand, the 8-oxodG concentration in cultured PC 12 cells was enhanced after dopamine treatment. This elevation may be below a threshold for manifestation as chromosomal damage.

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13 citations in Web of Science®
14 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:17 Jan 2011 17:57
Last Modified:05 Apr 2016 14:33
Publisher:Springer
ISSN:0300-9564
Publisher DOI:10.1007/s00702-010-0401-z
PubMed ID:20401731

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