Anticonvulsant and antioxidant actions of trimetazidine in pentylenetetrazole-induced kindling model in mice

Jain, Seema; Bharal, Nidhi; Khurana, Shilpi; Mediratta, Pramod Kumari; Sharma, Krishna K.

doi:10.1007/s00210-011-0606-1

Cited by 43 publications

(25 citation statements)

References 60 publications

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“…Results of the present study are in accordance with similar previous studies 10,23 . In the study by Jain et al 10 , the anti-convulsant activity of TMZ has been studied in an electroshock model of epilepsy with investigating the possible involvement of calcium channel blockage and using nimodipine and phenytoin.…”

Section: Discussionsupporting

confidence: 94%

“…Chronic effects of TMZ have been evaluated by measurement of brain MDA and reduced glutathione levels. Similar to our study, those authors have also reported a dose-dependent anticonvulsant effect for TMZ 23 . Our study differs from that study, because we used TMZ in higher doses and evaluated the acute effects of the drug and found more anti-convulsant effect when the drug was used in higher doses.…”

Section: Discussionsupporting

confidence: 93%

“…The authors have concluded that TMZ may have anti-convulsant activity through modulation of calcium channels. In another study by Jain et al 23 , the effect of TMZ on PTZ-induced epilepsy has been assessed by oxidative stress markers and seizure scores. In contrast to our study, TMZ has been administered for 5 weeks in that study.…”

Section: Discussionmentioning

confidence: 99%

“…The rats were kept under a 12 h light/dark cycle (light from 07.00 to 19.00), in quiet rooms, with [22][23][24] o C ambient temperature and provided free access to standard rat nutrients and purified drinking water ad libitum.…”

Section: Methodsmentioning

confidence: 99%

“…Despite the clearly-defined antiischemic effects of the TMZ, there are a limited number of studies in the literature on the potential effects of TMZ in epileptic seizures or convulsions 10,23 .…”

Section: Introductionmentioning

confidence: 99%

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Acute Administration of High Dose Trimetazidine Inhibits Pentylenetetrazol-Induced Seizures in Rats

Gürgül¹,

Erten

Gül³

et al. 2017

Cumhuriyet Medical Journal

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SUMMARYObjective: Resistant epilepsy is widely seen in clinical settings manipulate the researchers to pursuit novel anti-epileptic treatments. Although trimetazidine (TMZ) is commonly used in the treatment of angina and ischemic diseases, it is considered that the drug may be beneficial in the treatment of epileptic seizures and convulsions. We aimed to evaluate electrophysiologically the protective effects of high dose acute TMZ on epileptic seizures and convulsions in a rat model of epilepsy induced by pentilentetrazol (PTZ). Method: Forty-eight male Sprague-Dawley rats were used for the EEG evaluation (Group-A; n=24) and behavioral assessment (Group-B; n=24). Grup-A1 and Grup-B1 were determined as control group and given no medication. 35 mg/kg (Group-A2, -A3 and -A4) and 70 mg/kg (Group-B2, -B3 and -B4) of PTZ were administered intraperitoneally (ip.) so as to generate seizures and convulsions. Group-A2 and Group-B2 were treated with saline. 40 mg/kg (Grup-A3 and Grup-B3) and 80 mg/kg of TMZ (Group-A4 and Group-B4) were administered to the treatment groups by ip. Brain malondialdehyde (MDA) levels, spike-percentage values, Racine's Convulsion Scale (RCS) scores and "first myoclonic jerk (FMJ)" latencies of each rat were determined. Results: Brain MDA levels, spike-percentage values, RCS scores, and FMJ latencies of Group-A2 and Group-B2 were significantly increased compared to those of the control's (Grup-A1 and Grup-B1) (P<0.05 for all comparisons). However, in TMZ treated groups (Group-A3 and -A4; Group-B3 and -B4) the elevated values of these parameters were found to be significantly decreased (P<0.05 for all comparisons). Conclusions:This study has demonstrated that the high dose acute TMZ administration may prevent PTZ-induced seizures and convulsions in rats. Furthermore, it can be also said that TMZ has a neuroprotective effects on oxidative stress associated with PTZ. Therefore, it may be considered for use with therapeutic purposes of TMZ in resistant epilepsy patients in the future. Keywords: Electroencephalography (EEG), Epilepsy, Malondialdehyde, Pentylenetetrazol, Rat, Trimetazidine.ÖZET Amaç: İlaca-dirençli epilepsi, klinikte yaygın olarak görülen ve araştırmacıları yeni anti-epileptik tedavilerin saptanması için harekete geçiren bir durumdur. Trimetazidin (TMZ) anjina ve iskemik hastalıkların tedavisinde yaygın olarak kullanılmasına rağmen, epileptik nöbetler ve konvülsiyonların tedavisinde de yararlı olabileceği düşünülmektedir. Bu çalışmada, pentilentetrazol (PTZ) ile indüklenen bir sıçan epilepsi modelinde yüksek doz akut TMZ'nin epileptik nöbetler ve konvülsiyonlar üzerine koruyucu etkilerini elektrofizyolojik parametreler açısından değerlendirmeyi amaçladık. 381Yöntem: 48 adet erkek Sprague-Dawley cinsi sıçan EEG (Group-A; n=24) ve davranış analizlerinde (Group-B; n=24) kullanıldı. Grup-A1 ve Grup-B1 kontrol grubu olarak belirlendi ve ilaç verilmedi. 35 mg/kg (Group-A2, -A3 ve -A4) ve 70 mg/kg PTZ (Group-B2, -B3 ve -B4), nöbet ve konvülsiyon oluşturmak amacıyla, intraperitoneal olarak (i...

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Acute Administration of High Dose Trimetazidine Inhibits Pentylenetetrazol-Induced Seizures in Rats

Gürgül¹,

Erten

Gül³

et al. 2017

Cumhuriyet Medical Journal

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Characterization of anticonvulsant and antiepileptogenic potential of thymol in various experimental models

Sancheti

Shaikh

Chaudhari

et al. 2013

Naunyn-Schmiedeberg's Arch Pharmacol

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The present study was to investigate the anticonvulsant and antiepileptogenic potential of thymol. Anticonvulsant activity of thymol (5-100 mg/kg i.p.) was studied using maximal electroshock, pentylenetetrazole (PTZ), strychnine and 4-aminopyridine (4-AP) models. Thymol at the selected dose was also studied for its effect on locomotion. Antiepileptogenic property of thymol (5-25 mg/kg) was evaluated using PTZ-induced kindling model along with its effect on malondialdehyde and glutathione levels. Thymol (50 and 100 mg/kg, i.p.) showed anticonvulsant activity against maximal electroshock and pentylenetetrazole (66.66 and 83.33 % protection at 50 and 100 mg/kg, respectively) model but not against strychnine and 4-aminopyridine models. Thymol exhibited decreased locomotor activity in dose-dependent manner at the same dose range. Thymol at the dose of (25 mg/kg, i.p.) significantly decreased the seizure score, increased glutathione levels and decreased malondialdehyde levels in pentylenetetrazole-induced kindling model. Thymol exhibited significant anticonvulsant and antiepileptogenic property.

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Antiepileptogenic effects of borneol in pentylenetetrazole-induced kindling in mice

Tambe

Jain

Patil

et al. 2016

Naunyn-Schmiedeberg's Arch Pharmacol

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Borneol, a bicyclic monoterpene, can easily cross the blood brain barrier and was found to possess gamma amino butyric acid (GABA) modulatory effect. The present study was aimed at investigating the antiepileptogenic effect of borneol in the pentylenetetrazole (PTZ)-induced kindling besides its ability to suppress oxidative stress and neuroinflammatory marker, glial fibrillary acidic protein (GFAP). Repeated administration of a subconvulsive dose of PTZ (35 mg/kg, i.p.) on every alternate day for 4 weeks produced kindling in mice. Borneol (5, 10, and 25 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) were given as a pretreatment prior to each PTZ injection during the progression of kindling. Oxidative stress parameters such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and lipid peroxidation (LPO) were assessed at the end of the study. Neuronal damage was assessed by hematoxylin and eosin staining technique. GFAP was also evaluated in the hippocampus region of the brain by using immunohistochemistry. Borneol significantly suppressed the process of epileptogenesis in PTZ-kindled mice. The biochemical alterations induced by PTZ kindling were ameliorated in borneol-treated animals which was indicated by decreased LPO and increased SOD, GSH, CAT levels. The distinct neuronal damage observed in the kindled group was counteracted by borneol. Furthermore, it decreased the levels of GFAP which was manifested by reduced immunostaining. The above results are suggestive of the antiepileptogenic potential of borneol in the PTZ-induced kindling model of epilepsy, and thus, it could be a prospective molecule in the treatment of epilepsy.

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Anticonvulsant and antioxidant actions of trimetazidine in pentylenetetrazole-induced kindling model in mice

Cited by 43 publications

References 60 publications

Acute Administration of High Dose Trimetazidine Inhibits Pentylenetetrazol-Induced Seizures in Rats

Acute Administration of High Dose Trimetazidine Inhibits Pentylenetetrazol-Induced Seizures in Rats

Characterization of anticonvulsant and antiepileptogenic potential of thymol in various experimental models

Antiepileptogenic effects of borneol in pentylenetetrazole-induced kindling in mice

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