Effects of nimesulide on kainate-induced in vitro oxidative damage in rat brain homogenates.
BACKGROUND
The cyclooxygenase-2 inhibitor nimesulide is able to reduce kainate-induced oxidative stress in vivo. Here we investigate if this effect is mediated by the direct antioxidant properties of nimesulide using a well-characterized in vitro model of kainate toxicity.


RESULTS
Exposure of rat brain homogenates to kainate (12 mM) caused a significant (p < 0.01) increase in the concentrations of malondialdehyde and 4-hydroxy-alkenals and a significant (p < 0.01) decrease in sulfhydryl levels. High concentrations of nimesulide (0.6-1.6 mM) reduced the extent of lipid peroxidation and the decline in both total and non-protein sulfhydryl levels induced by kainate in a concentration-dependent manner.


CONCLUSIONS
Our results suggest that the neuroprotective effects of nimesulide against kainate-induced oxidative stress in vivo are not mediated through its direct free radical scavenging ability because the concentrations at which nimesulide is able to reduce in vitro kainate excitotoxicity are excessively higher than those attained in plasma after therapeutic doses.
Candelario-Jalil
Eduardo
E
Department of Pharmacology, University of Havana (CIEB-IFAL), Apartado Postal 6079, Havana City 10600, Cuba. ecjalil@infomed.sld.cu
Sonia León
Olga
O
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D013449:Sulfonamides; D008315:Malondialdehyde; D007608:Kainic Acid; C012655:nimesulide