Peripheral markers of oxidative stress in Parkinson's disease. The role of L-DOPA.
Oxidative stress plays a central role in the pathogenesis of Parkinson's disease (PD). L-DOPA, the gold standard in PD therapy, may paradoxically contribute to the progression of the disease because of its pro-oxidant properties. The issue, however, is controversial. In this study, we evaluated peripheral markers of oxidative stress in normal subjects, untreated PD patients and PD patients treated only with L-DOPA. We also measured platelet and plasma levels of L-DOPA, 3-O-methyldopa (the long-lasting metabolite of the drug), and dopamine. We found that isolated platelets of treated PD patients form higher amounts of 2,3-dihydroxybenzoate, an index of hydroxyl radical generation, than platelets of controls or untreated patients. In treated patients, platelet levels of 2,3-dihydroxybenzoate were positively correlated with platelet levels of L-DOPA, 3-O-methyldopa, and with the score of disease severity. Disease severity was correlated with platelet and plasma levels of L-DOPA, as well as with the daily intake of the drug. No significant differences in platelet levels of cytosolic and mitochondrial isoforms of the antioxidant enzyme superoxide dismutase were found between PD patients, either treated or untreated, and controls. Our findings lend further support to the hypothesis that L-DOPA might promote free radical formation in PD patients.
Martignoni
E
E
Center for Parkinson's Disease and Movement Disorders, Neurological Institute C. Mondino, University of Pavia, Italy.
Blandini
F
F
Godi
L
L
Desideri
S
S
Pacchetti
C
C
Mancini
F
F
Nappi
G
G
D000978:Antiparkinson Agents / Q000627:therapeutic use*; D015415:Biomarkers; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000097:blood; D005260:Female; D005841:Gentisates; D006801:Humans; D062385:Hydroxybenzoates / Q000097:blood; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D007980:Levodopa / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D012980:Sodium Salicylate / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000097:blood; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood
D000978:Antiparkinson Agents; D015415:Biomarkers; D005841:Gentisates; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; D014443:Tyrosine; D007980:Levodopa; C009135:2,3-dihydroxybenzoic acid; D013482:Superoxide Dismutase; C008404:3-methoxytyrosine; C010925:2,5-dihydroxybenzoic acid; D004298:Dopamine; D012980:Sodium Salicylate