Is Levodopa Neurotoxic in Vitro?
Levodopa is toxic to dopaminergic neurons in tissue culture (98–102). In these experiments, cells were exposed to levodopa concentrations that ranged from 100 to 250 μM for 1 to 5 days. Postulated mechanisms by which levodopa enhances cell death in these studies include the production of reactive oxygen radicals that, in turn, cause cell death by either apoptosis or necrosis. Walkinshaw and Waters (95) showed that levodopa, not dopamine, was toxic and that toxicity was inhibited by antioxidants. In general, the concentration of levodopa used in tissue culture experiments has exceeded, by a large margin, the plasma levels of levodopa that patients with PD are exposed to (5–50 μM) (103). Most in vitro experiments demonstrating levodopa toxicity have been conducted in neuronal cultures with few if any astrocytes – a major deficiency as astrocytes have been shown to prevent autooxidation (104) and in vivo may help protect against the potential oxidative toxicity of dopamine. Hydrogen perox
