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 (PT). L-DOPA, the gold standard in PD therapy, may paradoxically contribute to the progression of the disease because of its pra-oxidant properties. The issue, however, is controversial. In this study, we evaluated peripheral markers of oxidative stress in normal subjects, unheated 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 heated 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 unheated, and controls. Our findings lend further support to the hypothesis that L-DOPA might promote free radical formation in PD patients. (C) 1999 Elsevier Science Inc.