Early use of oleanolic acid provides protection against 6-hydroxydopamine induced dopamine neurodegeneration

Abstract

Oleanolic acid is a triterpenoid that has been shown to possess antioxidant properties. In this study we investigated the effects of oleanolic acid in a parkinsonian rat model. Unilateral 6-hydroxydopamine (6-OHDA) lesions were carried out on postnatal day (PND) 60 in 4 groups viz. (1) Rats that started oleanolic acid treatment 7 days prior to lesion. (2) Rats not treated with oleanolic acid. (3) Rats that started oleanolic acid treatment 1 day post-lesion. (4) Rats treated with oleanolic acid 7 days post-lesion. The degree of forelimb impairment was assessed using limb use asymmetry and forelimb akinesia tests. Neurochemical changes were assessed using a Dopamine ELISA kit and mitochondrial apoptosis was measured using a mitochondrial apoptosis detection kit. In this study, animals injected with 6-OHDA displayed forelimb use asymmetry that was ameliorated by treatment with oleanolic acid 7 days pre- and 1 day post-lesion. In the cylinder test, rats injected with 6-OHDA favored using the forelimb ipsilateral (unimpaired) to the lesioned hemisphere while rats treated with oleanolic acid used the forelimb contralateral (impaired) to the lesioned hemisphere significantly more. Rats treated with oleanolic acid 7 days pre- and 1 day post-lesion had more dopamine in the striatum than the non-treated or the 7 days after lesion rats. Similarly, 6-OHDA-induced membrane depolarization was decreased in rats that received oleanolic acid treatment pre- or immediately post-lesion. This suggests that early treatment with oleanolic acid protects dopamine neurons from the toxic effects of 6-OHDA.

Keywords: 6-hydroxydopamine; Dopamine; Neurodegeneration; Oleanolic acid; Oxidative stress; Parkinson׳s disease.