Levodopa and deprenyl treatment effects on peripheral indices of oxidant stress in Parkinson's disease

Although the cause of Parkinson's disease (PD) remains unexplained, oxidant stress is hypothesized as a major pathogenic factor. ^[1,2] The selective destruction of the substantia nigra is primarily responsible for the motor deficits that occur in this condition. This midbrain nucleus contains high concentrations of the catecholamine neurotransmitter dopamine, which is postulated to be a potential source of oxidant stress. This theoretically occurs as a consequence of two of the major routes by which dopamine is metabolized. Both enzymatic oxidation by monoamine oxidase (MAO) and nonenzymatic autoxidation of dopamine generate oxyradical byproducts. ^[1,2] As evidence, the lipid peroxidation product, malondialdehyde, is elevated in the degenerating substantia nigra of patients with PD. ^[3] It follows from this hypothesis that exogenous replacement therapy with the dopamine precursor levodopa is detrimental, since this elevates dopamine levels, potentially adding to the oxidant stress. ^[1,4]

Protection against one route of oxidative damage from dopamine (and levodopa therapy) may theoretically occur with the administration of deprenyl (selegiline). ^[1,2,5] This drug blocks the B form of MAO, one of the two major MAO isozymes. Indirect evidence from a large multicenter clinical trial ^[5] was interpreted as consistent with a neuroprotective effect from deprenyl and attributed to a reduction of oxidative damage generated via MAO metabolism of dopamine. ^[6] However, others suggest that the data are consistent with the action of deprenyl being merely symptomatic. ^[7,8]

The pathogenic process underlying PD may not, however, be confined to the brain or even the nervous system. Abnormalities in oxidative phosphorylation are present in circulating platelets ^[9-11] as well as muscle. ^[12-15] Two studies have reported elevated concentrations of the lipid peroxidation product malondialdehyde in serum or plasma of patients with PD. ^[16,17] Dermatologic findings (seborrheic dermatitis) are a recognized accompanying manifestation of PD, ^[18] an observation also consistent with extracerebral …