Isoeugenol prevents N-methyl-D-aspartate(NMDA)-induced neurotoxicity and convulsion

Isoeugenol prevents N-methyl-D-aspartate(NMDA)-induced neurotoxicity and convulsion

Isoeugenol, one of the phenylpropanoid derivatives has been known to inhibit the lipid peroxidation via scavenging effect on hydroxyl or superoxide radical production. We examined whether isoeugenol has a inhibitory effect against N-methyl-D-aspartate(NMDA)-, oxygen/glucose deprivation- and xanthine/xanthine oxidase(X/XO)-induced neurotoxicity or NMDA-induced $^{45}Ca^{+2}$ uptake elevation in primary mouse vertical cultures. We also evaluated whether isoeugenol exhibits inhibitory action on NMDA-induced convulsion in mice. Isoeugenol ($30{\sim}300{\mu}M$) attenuated NMDA- and X/XO-induced neurotoxicity by 11~85% and 83~92%, respectively. In the oxyge/glucose deprivation(60 min)-induced neurotoxicity, isoeugenol significantly(p<0.05) reduced by 32% at the maximal concentration. However, it failed to ameliorate NMDA-induced $^{45}Ca^{+2}$ uptake elevation. Isoeugenol(0.5g/kg, i.p.) delayed 6.5 times on the onset time of convulsion evoked by NMDA($0.1{\mu}g$) compared to that of control. These results suggest that the neuroprotective action of isoeugenol may be ascribed to the modulation of massive generation of reactive oxygen species(ROS) occurred during the ischemic or excitotoxic damage, not by directly affecting the NMDA receptor.