Effects of Repeated Levodopa Administration in an Animal Model of Parkinson's Disease: A Study of Oxidative Stress
Yagiela, Heather R.
Parkinson's disease (PD) is a neurodegenerative disorder resulting from decreased levels of the neurotransmitter dopamine. Patients with the disease suffer from muscle rigidity, tremors and balance impairment due to this loss. In order to counter the depletion of dopamine, the drug levodopa is commonly prescribed. However, some studies suggest that levodopa therapy promotes the production of free radicals in the brain, resulting in cellular damage due to oxidative stress. We believe that prolonged levodopa treatment does not result in oxidative stress. Using an animal model of PD with a unilateral 6-hydroxydopamine lesion, we administered carbidopallevodopa (5 mg/kg and 50 mg/kg, respectively) by intraperitonal injection for 17 consecutive days. An apomorphine screen was used to select animal subjects with a 90% or greater dopamine loss. Prior to the extraction of the striatum, ventral midbrain and cerebellum tissue, each animal received an i.p. injection of salicylate. Salicylate reacts with the free radicals of the brain producing dihydroxybenzoic acid (DHBA) in the form of 2,3-DHBA, whose level was measured using a high performance liquid chromatography system. The 2,3-DHBA to salicylate ratio was used to estimate hydroxyl radical production. No statistical difference was found in the 2,3-DHBA to salicylate ratios in any of the brain regions examined. These results suggest that repeated administration of levodopa does not promote the formation of free radicals in the brain and thus does not cause oxidative stress. This study implies that levodopa therapy is not hazardous to the health of patients and can be employed to treat the disease as deemed necessary.
vii, 26 p.
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