Uric acid is reduced in the substantia nigra in Parkinson's disease: effect on dopamine oxidation

Postmortem caudate and substantia nigra tissue samples from human parkinsonian patients (PD) and age-matched controls (NC) were analyzed for uric acid (UA), dopamine (DA), and ascorbic acid (AA) by HPLC/UV/ED. Uric acid and DA levels were significantly lower in the substantia nigra of PD by 54% and 85%, respectively. In the caudate, DA levels were significantly lower while UA levels were nonsignificantly reduced (0.10 < p < 0.05). Ascorbic acid levels were not significantly different from the controls in either brain region. Conditions favorable for oxidative stress were evaluated by measuring the oxidation of DA in individual brain homogenates. The rate constant for DA oxidation in control caudate was 0.34 x 10(-2) min-1 and in parkinsonian caudate was 4.20 x 10(-2) min-1. In control and parkinsonian substantia nigra DA oxidation rate constants were 2.82 x 10(-2) min-1 and 4.57 x 10(-2) min-1, respectively. Addition of UA or catalase to parkinsonian homogenate decreased the rate of DA oxidation, while addition of uricase to control homogenate increased the rate of DA oxidation. The data support the hypothesis that UA is decreased in nigrostriatal dopamine neurons in parkinsonian patients which contributes to an environment susceptible to oxidative stress, particularly through dopamine oxidation reactions.