Effects of nimesulide on kainate-induced in vitro oxidative damage in rat brain homogenates

Abstract

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.

Figure 1

Effect of different concentrations (1, 6 and 12 mM) of kainic acid (KA) on malonaldehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations in perfused rat brain homogenates following 20 min incubation. Values are means ± SEM of 3 experiments. Significant differences were determined by one-way ANOVA followed by Student-Newman-Keuls post-hoc test. *P < 0.05 and **P < 0.01 with respect to control.

Figure 2

Effect of Nimesulide (NIM) on malonaldehyde (MDA) and 4-hydroxy-alkenals (4-HDA) concentrations in perfused rat brain homogenates following 20 min incubation with 12 mM kainic acid (KA). Values are means ± SEM of 3 experiments. Significant differences were determined by one-way ANOVA followed by Student-Newman-Keuls post-hoc test. *P < 0.05 and **P < 0.01 with respect to KA 12 mM.