acute and sub-chronic anticonvulsant effects of edaravone on seizure induced by pentylenetetrazole or electroshock in mice, nitric oxide involvement

Background: edaravone is an anti-stroke medication that may have nitric oxide (no) modulating properties. this study evaluated the role of no in the acute and sub-chronic anticonvulsant effects of edaravone in murine models of seizures induced by intraperitoneal (ip) or intravenous (iv) injections of pentylenetetrazole (ptz) or electroshock (maximal electroshock seizure [mes]).methods: 132 male albino mice were randomly divided into 22 groups (n=6) and given ip injections of vehicle or edaravone either acutely or for eight days (sub-chronically). the seizure was induced by electroshock or ptz (ip or iv). the following edaravone doses were used: 7.5, 10, 12.5 (acute); 5, 7.5, 10 (sub-chronic) in ip ptz model; 5, 7.5, 10 in iv ptz model; and 5, 10 mg/kg in the mes. to evaluate no involvement, 216 mice were randomly divided into 36 groups (n=6) and pretreated with vehicle, edaravone, a non-specific nitric oxide synthase (nos) inhibitor: n(ω)-nitro-l-arginine methyl ester (l-name) (5 mg/kg), a specific nnos inhibitor: 7-nitroindazole (7-ni) (60 mg/kg), or a combination of edaravone plus l-name or 7-ni, either acutely or for eight days before seizure induction. doses of edaravone were as follows: in ip ptz model: 12.5 (acute) and 10 (sub-chronic); in iv ptz model: 10; and in the mes: 5 mg/kg. data were analyzed using the one-way analysis of variance (anova) followed by tukey’s test (spss 18). p≤0.05 was considered statistically significant.results: in the ip ptz model, edaravone increased time latencies to seizures (p<0.001), prevented tonic seizures, and death. edaravone increased the seizure threshold (p<0.001) in the iv ptz model and shortened the duration of tonic hind-limb extension (the) in the mes model (p<0.001). in comparison to mice treated with edaravone alone, adding l-name or 7-ni reduced seizure time latencies (p<0.001), reduced seizure threshold (p<0.001), and increased the duration (p<0.001).conclusion: edaravone (acute or sub-chronic) could prevent seizures by modulating no signaling pathways.