Effect of rofecoxib, a cyclo-oxygenase-2 inhibitor, on various biochemical parameters of brain associated with pentylenetetrazol-induced chemical kindling in mice.
Cyclo-oxygenase (COX) has been reported to play a significant role in neurodegeneration and other brain-related disorders. Recent studies have reported that COX plays a significant role in the pathophysiology of brain-related disorders and COX-2 inhibitors could be useful drug therapy in neurodegenerative disorders. The aim of the present study was to explore the possible role of COX and the effect of COX-2 inhibitor, rofecoxib in epilepsy. In the present study, kindling was induced in mice by chronic administration of a subconvulsive dose of pentylenetetrazol (PTZ, 40 mg/kg, i.p.) on every other day for a period of 15 days. Rofecoxib was administered orally daily 45 min before either PTZ or vehicle. The kindling score was recorded after PTZ administration. Seizure severity was measured according to a prevalidated scoring scale. Biochemical estimations were performed on the day 16 of PTZ treatment (24 h after the last dose of PTZ). Chronic treatment with selective COX-2 inhibitor, rofecoxib (2.0 and 5.0 mg/kg, p.o.) for 15 days showed significant decrease in PTZ-induced kindling score. Biochemical analysis showed that chronic treatment with PTZ significantly increased lipid peroxidation, nitrite levels (NO levels), and myeloperoxidase levels and decreased the reduced glutathione levels in brain homogenate. Chronic treatment with rofecoxib, a selective COX-2 inhibitor, significantly reversed the PTZ-induced kindling score as well as various biochemical alterations suggesting the use of COX-2 inhibitor rofecoxib in epilepsy. In conclusion, results of the present study suggested that COX-2 plays an important role in the pathophysiology of PTZ-induced kindling in mice and rofecoxib is protective against various biochemical alterations against PTZ-induced kindling in mice.
Dhir
Ashish
A
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
Naidu
Pattipati S
PS
Kulkarni
Shrinivas K
SK