Abstract

INFLUENCE OF SELECTIVE COX-2 INHIBITOR ETORICOXIB AGAINST MPTP INDUCED STRIATAL LESIONS IN THE RATS

ABSTRACT

Influence of selective COX-2 inhibitor Etoricoxib against MPTP induced striatal lesions in rats. Objectives: Previous studies have showed that there is increased cyclooxygenase-2 (COX-2) expression in neurodegenerative conditions like Parkinsonism and based on this contention we evaluated the effect of selective COX-2 inhibitor like Etoricoxib in 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated animal models, which is a standard model for chemically induced parkinsonism. Methods: The rats were divided in to 5 groups (n=6), two groups served as normal and sham control, one toxic control and two drug pre-treated group. The neurotoxin MPTP (32μmol in 5μl) was administered through intra-striatal route by stereotaxic surgery by using Hamilton micro syringe. The drug treatment group received Etoricoxib (10.8mg/kg, i.p) for 7 days. On 7 th day it received intrastriatal injection of MPTP and again drug treatment continued for 5 days. On 1st, 5th, 8th and12th day all rats were undergone for in vivo evaluation of locomotor activity and then the animal were sacrificed on 12th day for brain histology, and brain homogenates were also made using phosphate buffer for the evaluation of biochemical parameters. Results: The locomotor activity was decreased in the toxic control (MPTP) which was reversed significantly by the drug treated group. The inflammatory markers were evaluated, in which the Malondialdehyde (p<0.01), Nitrite (p<0.01), Myeloperoxide (p<0.01) levels were significantly decreased in the drug treated group compared to toxic control group which were the inflammatory markers. The Superoxide dismutase (p<0.01) and reduced glutathione levels (p<0.01) were increased by the drug treated groups compared to toxic control group which are involved in reducing oxidative stress and the morphological changes produced by the MPTP was restored by the drug treated group. Values are expressed as Mean ± SEM. Statistical analysis was done by using One way Anova. Conclusion: The results from the present study indicate that COX-2 inhibitors are exhibiting a protective effect on MPTP induced striatal lesions and the mechanism by which it acts is not clearly understood.

Keywords: Etoricoxib, MPTP, inflammation, Parkinsonism, Substantia nigra.