Neuroprotective role of Fenoprofen in experimental Parkinson’s disease

Y. Navya Reddya*, Ramya Krishna Pa, K. Rekha Ranib, Kuruva Jyothirmaib, R. Mohana Priyac Dr. M. N. Satish Kumara, T. Spurthid
aDepartment of Pharmacology, JSS College of Pharmacy (JSS University, Mysore), Udhagamandalam, Tamilnadu, India -643001
bDepartment of Pharmaceutics, CES College of Pharmacy, NH – 7, Chinnatekur, Kurnool, India – 518218.
cDepartmentof Pharmaceutical Chemistry, Dr. K .V Subbareddy Institute of Pharmacy, Kurnool, India – 518218.
dDepartment of Pharmacy Practice, CES College of Pharmacy, NH-7, Chinnatekur, Kurnool – 518218

A B S T R A C T
Parkinsonism is a neurodegenerative disorder of the Central Nervous system in which the dopaminergic cells of substania nigra degenerate and hence dopaminergic output to the corpus stratium and putamen fails Dopaminergic cell death occurs due to intra cellular elevation of calcium levels due to Oxidative stress caused by Free-radicals. Parkinsonism is induced experimentally by stereotaxic injection of 6-OHDA. Estimation of brain dopamine levels was performed by HPLC. Iron localization in substantia niagra was performed by PERL’S DAB method. The cytosolic and mitochondrial iron content was determined by performing Bleomycin assay. The caspase 3 activation was determined by spectrophotometric assay. Sequencing of COX-2 gene in rat midbrain was performed. When compared with 6-OHDA control group the Fenoprofen and Levodopa treated groups showed significant increase in brain dopamine levels. The cytosolic and mitochondrial iron levels were significantly decreased in Fenoprofen treated group when compared with 6-OHDA control. The COX-2 gene expression was prominent in 6-OHDA control group whereas it was significantly less in Fenoprofen treatment group. The Fenoprofen was tested for anti-Parkinson’s activity in 6-OHDA rat model. It showed reliable neuroprotection with respect to dopamine concentration, iron degeneration, inhibited caspase-3 activation and COX-2 gene expression. The investigations revealed that test drug could be a future molecule for treating clinical PD.
Keywords: Parkinsonism, Fenoprofen, Cytochrome C, COX-2 gene