title: Amelioration of L-Dopa-Associated Dyskinesias with Triterpenoic Acid in a Parkinsonian Rat Model.
abstract: 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.
authors.affiliation: Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.
authors.forename: Babongile C
authors.initials: BC
authors.lastname: Ndlovu
authors.affiliation: Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa.
authors.forename: Willie M U
authors.initials: WM
authors.lastname: Daniels
authors.affiliation: Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4000, South Africa. mabandlam@ukzn.ac.za.
authors.forename: Musa V
authors.initials: MV
authors.lastname: Mabandla
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000978:Antiparkinson Agents / Q000009:adverse effects*; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000209:etiology; D005121:Extremities / Q000503:physiopathology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D009068:Movement / Q000187:drug effects; D009828:Oleanolic Acid / Q000627:therapeutic use*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric
chemical_list: D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D007980:Levodopa; D009828:Oleanolic Acid; D016627:Oxidopamine; D002374:Catalase; D005978:Glutathione
keywords: Catalase; Dyskinesias; L-Dopa; Neuroprotection; Oleanolic acid; Parkinson’s disease