Trimetazidine exerts protection against increasing current electroshock seizure test in mice

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

doi:10.1016/j.seizure.2010.04.001

Cited by 13 publications

(19 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

“…Thus, TMZ was concluded to decrease the oxidative stress dose-dependently in PTZ-induced epilepsy model in rats and it can be suggested that the TMZ has a protective effect on oxidative damage associated with PTZ in brain. Although the protective effects of TMZ on oxidative tissue damage have been shown in various experimental studies [40][41][42][43][44] , there are only a few studies investigating the efficacy of TMZ on this issue in brain 10,46 .…”

Section: Discussionmentioning

confidence: 99%

“…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. The authors have concluded that TMZ may have anti-convulsant activity through modulation of calcium channels.…”

Section: Discussionmentioning

confidence: 99%

“…Trimetazidine (TMZ) is a piperazine-derived lipophilic agent came into focus with use in angina treatment and for ischemic events 10 . The drug exerts anti-ischemic effect without inducing hemodynamic changes 11 .…”

Section: Introductionmentioning

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%

See 4 more Smart Citations

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

Gürgül¹,

Erten

Gül³

et al. 2017

Cumhuriyet Medical Journal

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Gürgül¹,

Erten

Gül³

et al. 2017

Cumhuriyet Medical Journal

View full text Add to dashboard Cite

show abstract

Beneficial effect of trimetazidine on folic acid‐induced acute kidney injury in mice: Role of HIF‐1α/HO‐1

Abdelrahman

Abdelsalam

Zaghloul

2022

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Acute kidney injury (AKI) is a complex syndrome associated with a decrease in renal function and a significant impact on patient outcomes. Injection of folic acid (FA) in mice is used for studying the pathogenesis of AKI. This study investigated the impact of trimetazidine (a metabolic modulator-antianginal drug; TMZ), against FA-induced AKI. AKI was induced by FA (250 mg/kg, ip) in mice. Two doses of TMZ were administered orally for 10 days. Administration of TMZ at a high dose (20 mg/kg) exhibited significant decreases in the renal somatic index (RSI), serum levels of lactate dehydrogenase (LDH), creatinine (Cr), blood urea nitrogen (1), and proteins level in urine. Moreover, TMZ significantly increased creatinine clearance (CCr), serum albumin, urine creatinine, and urine urea levels.This improvement in markers of kidney damage was associated with marked renal antioxidant effects (↓NO and ↓lipid peroxidation, normalized reduced glutathione (GSH) level and superoxide dismutase (SOD) activity, and increased HIF-1α/HO-1 level). Furthermore, TMZ significantly decreased FA-induced expression of MPO and inflammatory cytokine IL-18, TNF-α, and NF-κB p65 subunit. Renal apoptosis, along with apoptotic markers, were enhanced by FA injection and suppressed by TMZ administration (↓Caspase-3, ↓Bax, and ↑Bcl2 expression). Finally, TMZ amended FA-induced histopathological changes in kidneys. By mitigating functional alteration, oxidative stress, and preventing the development of inflammatory and apoptosis signals, TMZ provides dosedependent defense against FA-induced AKI mainly via stimulation of hypoxia-inducible factor-1 alpha (HIF-1α)/heme oxygenase-1 (HO-1) pathway.

show abstract

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

Jain

Bharal

Khurana

et al. 2011

Naunyn-Schmied Arch Pharmacol

Self Cite

View full text Add to dashboard Cite

The present study was carried out to investigate the effect of trimetazidine on the course of pentylenetetrazole (PTZ)-induced chemical kindling and oxidative stress markers in PTZ-kindled mice. Kindling was induced by repeated injections of a subconvulsive dose of PTZ (30 mg⁄kg, i.p.) on alternate days for 5 weeks or until stage 4 of the seizure score was evoked on three consecutive administrations. Trimetazidine was administered daily in three doses (5, 10 and 20 mg/kg) per orally (p.o.) along with alternate-day PTZ. Following PTZ kindling, oxidative stress parameters, i.e. levels of malondialdehyde (MDA) and reduced glutathione (GSH), were assessed in isolated homogenized whole brain tissue. The results showed that PTZ treatment progressively increased the seizure score in control mice. Biochemical analysis revealed a significant increase in MDA levels and decreased GSH levels in the brain homogenate of PTZ-kindled mice. Daily treatment with trimetazidine in doses of 10 and 20 mg/kg significantly decreased the PTZ-induced seizure score. However, a low dose of trimetazidine (5 mg/kg) failed to improve the seizure score. Pretreatment of trimetazidine in all doses showed an ameliorating effect on biochemical alteration induced by PTZ treatment. The results of the present study indicate the potential anticonvulsant activity of trimetazidine against PTZ-induced kindling in mice.

show abstract

Trimetazidine exerts protection against increasing current electroshock seizure test in mice

Cited by 13 publications

References 26 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

Beneficial effect of trimetazidine on folic acid‐induced acute kidney injury in mice: Role of HIF‐1α/HO‐1

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

Contact Info

Product

Resources

About