Protective effect of rofecoxib and nimesulide against intra-striatal quinolinic acid-induced behavioral, oxidative stress and mitochondrial dysfunctions in rats

Harikesh Kalonia, Puneet Kumar, Anil Kumar, Bimla Nehru
Neurotoxicology 2010, 31 (2): 195-203
Role of cyclooxygenase (COX) enzyme has been well documented in both physiological and pathological conditions. COX-1 and COX-2 converts arachidonic acid into prostaglandins. Non-selective inhibition of COXs produces undesirable effects, whereas selective COX-2 inhibition produces protective effects in various inflammatory diseases. Recently, cyclooxygenase (COX) inhibitors have been implicated as a neuroprotectant in the treatment of various neurodegenerative diseases. Quinolinic acid is an endogenous excitotoxin that causes neurotoxicity in diverse areas of the brain and produces motor dysfunction. Present study is an attempt to investigate the possible role of COX inhibitors (selective COX-2 inhibitor and preferential COX-2 inhibitors) against quinolinic acid-induced behavioral, oxidative stress and mitochondrial enzyme complex alterations in rats. Intra-striatal administration of quinolinic acid (300 nmol) caused significant reduction in body weight (9%), motor in-coordination, oxidative damage [increased MDA (100%), nitrite concentration (195%), depleted SOD (71%), catalase levels (70%)] and alteration in mitochondrial enzyme complex activity (decreased complex I (50%), II (50%) and IV(62%)) as compared to sham operated animals. Chronic treatment with rofecoxib (10 and 20 mg/kg, p.o.) and nimesulide (10 and 20mg/kg, p.o.) significantly attenuated quinolinic acid-induced behavioral and biochemical alterations as compared to quinolinic acid 300 nmol treated group. Further, rofecoxib (10, 20 mg/kg) and nimesulide (20 mg/kg) significantly restored mitochondrial enzyme complex activities in striatum as compared to quinolinic acid 300 nmol treated group. Present study highlights the therapeutic potential of cyclooxygenase inhibitors against quinolinic acid induced neurotoxicity.

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