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Moezi, Leila, Pirsalami, Fatema, Dastgheib, Mona, Oftadehgan, Somayeh, Purkhosrow, Azar, Sattarinezhad, Elahe. (1402). Acute and Sub-chronic Anticonvulsant Effects of Edaravone on Seizure Induced by Pentylenetetrazole or Electroshock in Mice, Nitric Oxide Involvement. سامانه مدیریت نشریات علمی, 48(3), 329-340. doi: 10.30476/ijms.2022.94177.2544
Leila Moezi; Fatema Pirsalami; Mona Dastgheib; Somayeh Oftadehgan; Azar Purkhosrow; Elahe Sattarinezhad. "Acute and Sub-chronic Anticonvulsant Effects of Edaravone on Seizure Induced by Pentylenetetrazole or Electroshock in Mice, Nitric Oxide Involvement". سامانه مدیریت نشریات علمی, 48, 3, 1402, 329-340. doi: 10.30476/ijms.2022.94177.2544
Moezi, Leila, Pirsalami, Fatema, Dastgheib, Mona, Oftadehgan, Somayeh, Purkhosrow, Azar, Sattarinezhad, Elahe. (1402). 'Acute and Sub-chronic Anticonvulsant Effects of Edaravone on Seizure Induced by Pentylenetetrazole or Electroshock in Mice, Nitric Oxide Involvement', سامانه مدیریت نشریات علمی, 48(3), pp. 329-340. doi: 10.30476/ijms.2022.94177.2544
Moezi, Leila, Pirsalami, Fatema, Dastgheib, Mona, Oftadehgan, Somayeh, Purkhosrow, Azar, Sattarinezhad, Elahe. Acute and Sub-chronic Anticonvulsant Effects of Edaravone on Seizure Induced by Pentylenetetrazole or Electroshock in Mice, Nitric Oxide Involvement. سامانه مدیریت نشریات علمی, 1402; 48(3): 329-340. doi: 10.30476/ijms.2022.94177.2544

Acute and Sub-chronic Anticonvulsant Effects of Edaravone on Seizure Induced by Pentylenetetrazole or Electroshock in Mice, Nitric Oxide Involvement

Iranian Journal of Medical Sciences
مقاله 11، دوره 48، شماره 3، مرداد 2023، صفحه 329-340    اصل مقاله (1.57 M)
نوع مقاله: Original Article(s)
شناسه دیجیتال (DOI): 10.30476/ijms.2022.94177.2544
نویسندگان
Leila Moezi؛ Fatema Pirsalami؛ Mona Dastgheib؛ Somayeh Oftadehgan؛ Azar Purkhosrow؛ Elahe Sattarinezhad*
Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
چکیده
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.
کلیدواژه‌ها
Edaravone؛ Epilepsy؛ Pentylenetetrazole؛ Electroshock؛ Nitric oxide
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