Amelioration of L-Dopa-Associated Dyskinesias with Triterpenoic Acid in a Parkinsonian Rat Model

摘要

Levo-Dopa (l-Dopa) is widely used for the oral treatment of Parkinson's disease. However, chronic treatment with l-Dopa produces abnormal involuntary movements (AIMs) known as dyskinesias. In this study, commercially available oleanolic acid (OA) that has been previously shown to ameliorate the toxic effects of 6-hydroxydopamine (6-OHDA) in preconditioning studies was used to treat AIMs in a rat model for Parkinson's disease. The forelimb-use asymmetry test was used to measure Parkinson's disease-associated motor impairment. AIMs were measured after 21 days of l-Dopa administration. Glutathione levels were measured in blood, and catalase levels were measured in the substantia nigra and striatum of both the left and right hemispheres. We found that l-Dopa alone as well as l-Dopa and OA combination treatment attenuated the limb-use asymmetry caused by the unilateral injection of 6-OHDA. Chronic l-Dopa administration produced AIMs which were attenuated by treatment with OA. Catalase concentration decreased significantly in the striatum but not in the substantia nigra of the lesioned hemisphere. l-Dopa alone as well as the combined l-Dopa and OA treatment ameliorated the effects of 6-OHDA on catalase concentration. However, intervention with l-Dopa alone as well as with l-Dopa and OA did not affect plasma glutathione concentration. These results suggest that OA administration enhances the effect of catalase on reactive oxygen species following 6-OHDA injection. OA may provide possibilities as an adjunct treatment to prevent or attenuate the development of AIMs following chronic l-Dopa treatment in Parkinson's disease.