No increased chromosomal damage in L-DOPA-treated patients with Parkinson's disease: a pilot study.
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.
Oli
Rajaraman Gnana
RG
Department of Toxicology, University of Wuerzburg, Versbacher Strasse 9, 97078 Wuerzburg, Germany.
Fazeli
Gholamreza
G
Kuhn
Wilfried
W
Walitza
Susanne
S
Gerlach
Manfred
M
Stopper
Helga
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects*; D002478:Cells, Cultured; D002853:Chromatography, Liquid / Q000379:methods / Q000706:statistics & numerical data; D002875:Chromosomes / Q000187:drug effects* / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000379:methods; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D036681:Fluorescence Recovery After Photobleaching / Q000379:methods; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy; D010865:Pilot Projects; D051381:Rats; D053719:Tandem Mass Spectrometry / Q000379:methods
D000978:Antiparkinson Agents; D004791:Enzyme Inhibitors; D007980:Levodopa; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
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