The effect of levodopa on the blood antioxidant system and metabolome in patients with Parkinson's disease.

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.