Anticonvulsant and Antioxidant Effects of Pitavastatin Against Pentylenetetrazol-Induced Kindling in Mice

Abstract

Purpose: The pleiotropic effects of statins (antioxidant and anti-inflammation) have been reported by previous studies. Therefore, we aimed to determine whether pitavastatin has protective effects against pentylenetetrazol (PTZ)-induced kindling in mice and also whether pitavastatin improves the brain antioxidant capacity and attenuates the oxidative injuries in kindled mice. Methods: Twenty-four mice were randomly divided into four groups (each group n=6); control, PTZ-kindling and PTZ-kindled rats treated with pitavastatin (1&4 mg/kg). PTZ kindling seizures were induced by repetitive intraperitoneal injections of PTZ (65 mg/kg) every 48 hours till day twenty-one. Animals received daily oral pitavastatin for twenty-one days. Latency, score and duration of the seizures were recorded. The activities of catalase (CAT) ad superoxide dismutase (SOD), and likewise the contents of malondialdehyde (MDA) and nitrate were assessed in the brains of all rats. Results: There was a progressive reduction in latency of the kindled rats in the next injections of PTZ. Pitavastatin reduced this value (latency) particularly at higher dose. Seizures duration and score also decreased in treatment groups. SOD and CAT activities significantly decreased in PTZ-kindling group by 62% and 64%, respectively, but pitavastatin did not significantly change the SOD and CAT activities. Brain MDA and nitrate significantly increased in PTZ-kindling group by 53% and 30%, respectively. Pitavastatin at higher dose significantly decreased the MDA and nitrate contents of PTZ-kindling rats by 45% and 32%, respectively. Conclusion: Our findings revealed that pitavastatin can improve the behavioral expression of the PTZ-kindling rats and attenuate the seizure-induced oxidative/nitrosative damage.

Chemogenetic Activation of Feed-Forward Inhibitory Parvalbumin-Expressing Interneurons in the Cortico-Thalamocortical Network During Absence Seizures

“…The latency to first seizure after PTZ treatment (on day 1) was within 5 min in PV Cre /Gq-DREADD and non-DREADD mice, which is consistent with other published studies in mice (Keskil et al, 2001;Medina et al, 2001;Ilhan et al, 2006;Erbayat-Altay et al, 2008;Nassiri-Asl et al, 2009;Koutroumanidou et al, 2013;Faghihi and Mohammadi, 2017;de Freitas et al, 2018). These studies have shown that irrespective of dose of PTZ (20-80 mg/kg, i.p.…”

Inhibitory interneuron classification, function and dysfunction in neural network

“…The latency to first seizure after PTZ treatment (on day 1) was within 5 min in PV Cre /Gq-DREADD and non-DREADD mice, which is consistent with other published studies in mice (Keskil et al, 2001;Medina et al, 2001;Ilhan et al, 2006;Erbayat-Altay et al, 2008;Nassiri-Asl et al, 2009;Koutroumanidou et al, 2013;Faghihi and Mohammadi, 2017;de Freitas et al, 2018). These studies have shown that irrespective of dose of PTZ (20-80 mg/kg, i.p.…”

Polish Journal of Veterinary Sciences

“…To elucidate the effect of VAL and 7-NI against ROS generation, plasma level of SOD antioxidant enzyme was determined. Kola et al (2018) reported that oxidative enzymes markers were increased while antioxidative stress enzymes (including SOD) were reduced in cortex of PTZ kindling model and SOD activity also decreased in brain tissue in PTZ-kindling mice model (Faghihi and Mohammadi 2017). Kim et al (2015) reported that Valeriana radix extract (100 mg/kg for five days) didn't affect SOD level of plasma in stressed mice.…”