Neuroprotective effect of nimesulide, a preferential COX-2 inhibitor, against pentylenetetrazol (PTZ)-induced chemical kindling and associated biochemical parameters in mice.

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Citation

Dhir A, Naidu PS, Kulkarni SK

Neuroprotective effect of nimesulide, a preferential COX-2 inhibitor, against pentylenetetrazol (PTZ)-induced chemical kindling and associated biochemical parameters in mice.

Seizure. 2007 Dec;16(8):691-7. Epub 2007 Jul 2.

PubMed ID
17604186 [ View in PubMed
]
Abstract

Brain cyclooxygenases (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-selective 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 role 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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AntrafenineProstaglandin G/H synthase 2ProteinHumans
Unknown
Inhibitor
Details
NaproxenProstaglandin G/H synthase 2ProteinHumans
Yes
Inhibitor
Details