Effect of preferential cyclooxygenase-2 (COX-2) inhibitor against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced striatal lesions in rats: behavioral, biochemical and histological evidences.
Cyclooxygenase (COX) isoenzyme is known to play an important role in the pathophysiology of Parkinson's disease. The present study evaluated the neuroprotective effect of nimesulide, a preferential COX-2-inhibitor against 1-methyl-4-phenyl-1,2,3,6-tertahydropyridine (MPTP)-model of Parkinson's disease. Intrastriatal administration of MPTP (32 micromol in 2 microl) produced a significant decrease in the locomotor activity. Biochemical investigation of striatal region revealed a significant enhancement in the oxidative stress as evidenced by increased lipid peroxidation levels, nitrite levels and myeloperoxidase activity along with depleted antioxidant pool (reduced glutathione and superoxide dismutase levels) and reduced redox (GSH/GSSG) ratio. MPTP administration also showed significant mitochondrial complex-I inhibition and reduction in the mitochondrial viability. Histological examination of the MPTP-treated brain sections revealed alteration in the histo-architecture as well as undifferentiated bodies of varying contour and lesions. Chronic administration of nimesulide (5 or 10 mg/kg, po) for 12 days, significantly reversed the behavioral, biochemical, mitochondrial and histological alterations induced by MPTP. In conclusion, the findings of the present study implicate the possible neuroprotective potential of nimesulide in MPTP-treated rats and thus highlight the therapeutic potential of COX-inhibitors in treatment of Parkinson's disease.
Gupta
Amit
A
Pharmacology Division, University Institute of Pharmaceutical Sciences Panjab University, Chandigarh 160 014, India.
Dhir
Ashish
A
Kumar
Anil
A
Kulkarni
S K
SK
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D020267:MPTP Poisoning / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009498:Neurotoxins / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000627:therapeutic use*
D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D018696:Neuroprotective Agents; D009498:Neurotoxins; D013449:Sulfonamides; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D051546:Cyclooxygenase 2; C012655:nimesulide