Antiparkinsonian Effect of Pioglitazone through Effective Antioxidative Property in Mptp Mice Model of Parkinson’s Disease

Oxidative stress plays a vital role in dopaminergic neurodegeneration of Parkinson’s disease (PD). However, an antidiabetic drug, pioglitazone had shown a positive effectagainst oxidative stress to treat nervous unrest. Objective of this study is to evaluate the protective effect of Pioglitazone (25mg/kg/p.o) against 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model of PD. The PD induced animals were treated orally with 25 mg/kg bodyweight of Pioglitazone hydrochloride for a period of 2 weeks. The Mice in control and experimental groups were subjected to various behavioural tests like rota rod, stride length measurement, olfactory, inverted grip and open-field tests etc. At the end of the experimental period, mice were sacrificed and the mid brain region was isolated. Striatal dopamine level was estimated and Tyrosine hydroxylase positive (TH + ) cells were counted by flow cytometry and monoamine oxidase levels estimated by flourimetry. Histopathological studies were performed on mid brain sections. The levels of monoamine oxidase B, total monoamine oxidase levels, lipid peroxidation (LPO), Reactive Oxygen Species (ROS), reduced glutathione (GSH), glutathione reductase (GR) and glutathione peroxidase (GPx) were analysed. The Dopamine level lowered in MPTP mice was significantly and dose dependently increased with Pioglitazone treatment. TH + cell count was significantly lowered in MPTP mice while it was increased with Pioglitazone treatment. H&E stained sections of mid brain of PD mice revealed glial cell infiltration and occasional areas of dystrophic calcification. The histological findings observed in the brain sections of 25mg/kg pioglitazone treatment group were comparable to that of the control group. Oxidative stress (elevated LPO, increased levels of monoamine oxidase B, total monoamine oxidase and decreased activities of antioxidants (GSH, ROS, GR and GPx)) observed in MPTP mice were significantly ameliorated by Pioglitazone treatment. These results specify the anti-parkinsonian effect of Pioglitazone and this neuro-protective effect was executed partly through its anti-oxidant property.