Neuroprotective effect of nimesulide, a preferential COX-2 inhibitor, against pentylenetetrazol (PTZ)-induced chemical kindling and associated biochemical parameters in mice.
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.
Dhir
Ashish
A
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
Naidu
Pattipati S
PS
Kulkarni
Shrinivas K
SK
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001923:Brain Chemistry / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy*; D005978:Glutathione / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D009573:Nitrites / Q000378:metabolism; D010433:Pentylenetetrazole; D009195:Peroxidase / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage*; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D009573:Nitrites; D013449:Sulfonamides; D009195:Peroxidase; D005978:Glutathione; C012655:nimesulide; D010433:Pentylenetetrazole