Effects of atorvastatin and metformin on development of pentylenetetrazole-induced seizure in mice

Abstract

Recent studies have shown that statins and Metformin may have beneficial effects on seizure through different mechanisms. In the current study, we investigated whether Metformin, Atorvastatin, and concomitant uses of them have beneficial effects on pentylenetetrazole (PTZ)-induced kindling. Adult male C57BL/6 mice were randomly divided into four experimental groups with seven mice in each group. Group 1, control group; group 2, received Metformin (200 mg/kg, i.p); group 3, received Atorvastatin (10 mg/kg, i.p.); group 4, received Atorvastatin (10 mg/kg, i.p.) plus Metformin (200 mg/kg, i.p.). Twenty minutes after injection of the mentioned drugs, the experimented mice received 37/5 mg/kg of PTZ intraperitoneally on alternating days. Then the convulsive behavior signs were evaluated for 20 min after each PTZ injection. There were significant differences in the stage 2 latency parameter among group 2 (p ¼ 0.033, F ¼ 8.46)/group 3 (p ¼ 0.032, F ¼ 10.42)/group 4 (p ¼ 0.008, F ¼ 24.57) as compared to the control group, while no significant differences were found comparing only group 2,3, and 4 with eachother excluding the control group. Pretreatment with Atorvastatin (p ¼ 0.002, F ¼ 33), Atorvastatin þ Metformin (p ¼ 0.006, F ¼ 20.77), and Metformin alone increased stage 5 latency as compared to the PTZ group, significantly. Also, our results have shown that pretreatment with Atorvastatin (p ¼ 0.013, F ¼ 14.48), Metformin (p ¼ 0.015, F ¼ 16.67), and concomitant usage of them significantly decreased stage 5 duration as compared to the control group. Our findings clearly demonstrate that concomitant use of Metformin and Atorvastatin has no more protective effect against the development of kindling as compare to these drugs alone. Thus, we concluded that, these drugs may inhibit kindling via a similar mechanism and we suggested that it is probably through regulation of autophagy.

Metformin as a potential therapeutic for neurological disease: mobilizing AMPK to repair the nervous system

“…Treating rats with pilocarpine hydrochloride-induced epilepsy for 5 days with metformin decreased levels of p-mTOR protein and elevated levels of p-AMPK protein along with having anti-epileptic and anti-convulsant effects [ 106 ]. It has recently been suggested that mTOR regulation of autophagy may be responsible for the anti-convulsant effects [ 107 ]. Metformin treatment also suppressed expression of BDNF and its receptor, trk B, which are hyper-expressed in the epileptic brain and represent a pathological signaling cascade in mesial temporal lobe epilepsy [ 106 , 108 ].…”

Beneficial Effects of Metformin on the Central Nervous System, with a Focus on Epilepsy and Lafora Disease

“…Recently, it has been described that metformin reduces CHOP expression and apoptosis induced by status epilepticus in rats [68]. The beneficial effects of metformin on this model could also be due to an improvement in autophagy [69]. Additional reports indicate that AMPK activation by metformin decreases seizure susceptibility, facilitates seizure termination, and reduces the number and duration of seizures in a PTZ-induced epilepsy model [70].…”

Anticonvulsant effects of ivermectin on pentylenetetrazole- and maximal electroshock-induced seizures in mice: the role of GABAergic system and KATP channels

“…and intraperitoneal (i.p.) injection of PTZ models in our current work, which have been utilized widely as the lab assessments to evaluate the anti-seizure effects of medication and to develop new antiepileptic therapies [ 40 , 41 , 42 , 43 , 44 ]. Similarly, the maximal electroshock-induced tonic-clonic seizure is the most severe electroshock convulsive response induced by supramaximal electrical stimulation currents.…”