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. doi: 10.1016/j.seizure.2007.05.016. Epub 2007 Jul 2.

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.

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Brain Chemistry / drug effects*
  • Cyclooxygenase Inhibitors / administration & dosage*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Interactions
  • Epilepsy / chemically induced
  • Epilepsy / drug therapy*
  • Glutathione / metabolism
  • Kindling, Neurologic / drug effects*
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Nitrites / metabolism
  • Pentylenetetrazole
  • Peroxidase / metabolism
  • Sulfonamides / administration & dosage*
  • Time Factors

Substances

  • Cyclooxygenase Inhibitors
  • Nitrites
  • Sulfonamides
  • Peroxidase
  • Glutathione
  • nimesulide
  • Pentylenetetrazole