Byline: Nilesh. Ambhore, Maruthi. Prasanna, A. Antony, M. Satish Kumar, K. Elango
Background: Mitochondrial damage and oxidative stress plays important role in Parkinson's disease (PD). Mitochondria are very crucial part in the cell and have many cellular functions including the generation of ATP and intracellular calcium (Ca [sup]2+ ) homeostasis. Mitochondria also contribute in the formation of reactive oxygen species (ROS) and activating the programmed cell death response, apoptosis. Usually ROS is eliminated by antioxidants present in body, but in case of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induction all the antioxidants become ineffective. Aim: The present study investigated the effects of the non selective cyclooxygenase (COX) inhibitor aspirin and L-type calcium channel inhibitor nimodipine in the prevention of motor impairments and observed anti-oxidant effects in rats after induction of early phase of Parkinson's disease by using neurotoxin MPTP. Materials and Methods: The PD was induced in animals by single injection of MPTP. After 48 hrs of induction animals were treated with aspirin and nimodipine for 60 days, then behavioral, biochemical and antioxidant parameters were evaluated to examine the effectiveness of treatment. Statistical analysis was carried out by using one-way ANOVA followed by Bonferroni multiple comparisons test. Results: The treatment with combination (Aspirin 50mg/kg, Nimodipine 30mg/kg) showed significant (P < 0.001) increase in brain dopamine level, improves the complex I activity and also ameliorate the amount of antioxidant enzymes like superoxide dismutase (SOD), glutathione reductase (GSH), catalase (CAT) and decrease in lipid peroxidation. Conclusions : These results strongly suggest that combination shows a good neuroprotective effect compared to single treatment on motor, biochemical and antioxidant parameters in early phase of Parkinson's disease.
Parkinson's disease (PD) is a progressive neurodegenerative disease due to loss of nigrostriatal dopaminergic neurons. The pathogenesis of PD remains obscure, but there is increasing evidence that impairment of mitochondrial function, oxida-tive damage, and inflammation are contributing factors. Some articles shown that deficiency or damage of complex I activity of the mitochondrial electron transport chain can lead to PD. Also there is evidence for in-creased numbers of activated microglia in both PD postmortem tissues as well as in animal models of PD. These activated microglia and mitochondrial dysfunctions may both contribute to oxidative damage in PD. There are number of therapeutic targets available which can target inflammation and mitochondrial dysfunction and can be efficacious in the MPTP model of PD. [sup]
The neurotoxin MPTP has been shown to induce parkinsonism in man and non-human primates. Hypotheses concerning the mechanism of action of MPTP have been related to the pathogenesis of nigral cell death in Parkinson's disease. For instance, alterations of calcium influxes have been reported to be implicated in both MPTP-induced Parkinsonism and Parkinson's disease. [sup]
Several factors including inflammation are believed to be involved in the pathogenesis of this disease. The enzyme cyclooxygenase as well as inflammatory mediators such as nitric oxide have been reported to be increased in PD. [sup], In the MPTP induced animal model of PD, mechanisms mediating inflammatory reactions are reported to contribute to the neuronal...