Journal
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
Volume 16, Issue 8, Pages 691-697Publisher
W B SAUNDERS CO LTD
DOI: 10.1016/j.seizure.2007.05.016
Keywords
cyclooxygenase; epilepsy; kindling; nimesulide; pentylenetetrazol
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Brain cyctooxygenases (COX), the rate-Limiting enzyme in prostaglandin synthesis, is rapidly and transiently induced by convulsions in hippocampal and cortical neurons. Previous studies have explored the protective effect of naproxen (non-setective COX-inhibitor) or rofecoxib (selective COX-2 inhibitor) against chemical kindling in mice. With this background, the present study was designed to explore the possible effect of nimesulide (a preferential COX-2 inhibitor) against pentylenetetrazol (PTZ)-induced kindling epilepsy in mice. To induce kindling, PTZ was injected in a subconvulsive dose (40 mg/kg, i.p.) every other day for 15 days. Nimesulide (2.5 or 5 mg/kg, p.o.) was administered each day 45 min before either PTZ or vehicle challenge. The intensity of kindling was assessed immediately after PTZ administration according to a prevalidated scoring scale. On 16th day i.e. 24 h after the Last dose of PTZ, animals were sacrificed and various biochemical parameters were assessed in the whole brain. Compared with normal control group, PTZ-kindled mice had significantly higher Levels of malondialdehyde, nitrite, myeloperoxidase but had lower levels of reduced glutathione in the whole brain homogenate. Chronic treatment with nimesulide (2.5 or 5 mg/kg, p.o.) for 15 days showed significant decrease in kindling score and could play a rote in controlling the accompanying biochemical alterations due to PTZ. These results suggested that nimesulide, a preferential COX-2 inhibitor offered neuroprotection against PTZ-induced kindling in mice. (c) 2007 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
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