International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
Bootstrap Slider

Indexed and Abstracted in: SCOPUS, Crossref, CAS Abstracts, Publons, CiteFactor, Open J-Gate, ROAD, Indian Citation Index (ICI), Indian Journals Index (IJINDEX), Internet Archive, IP Indexing, Google Scholar, Scientific Indexing Services, Index Copernicus, Science Central, Revistas Medicas Portuguesas, EBSCO, BOAI, SOROS, NEWJOUR, ResearchGATE, Ulrich's Periodicals Directory, DocStoc, PdfCast, getCITED, SkyDrive, Citebase, e-Print, WorldCat (World's largest network of library content and services), Electronic Journals Library by University Library of Regensburg, SciPeople.

Search Articles

Track manuscript

Readers around the world

Full Html

IJCRR - vol 05 issue 19, October, 2013

Pages: 61-65

Date of Publication: 19-Oct-2013

Print Article   Download XML  Download PDF


Author: Nayak V., Adiga S., Poornima B.M., Sharma R., Garg A., Shetty M., Kamath S., Hegde M., Koshy S.S.

Category: Healthcare

Abstract:Introduction: Statins, the widely used hypolipidemics drugs have a number of pleotropic effects. Objective: To study the effect of chronic administration of atorvastatin, simvastatin and lovastatin on maximal electroshock and pentylenetetrazole induced seizures in Wistar rats. Material and Methods: After obtaining institutional animal ethics committee clearance the study was conducted in male wistar rats. The animals were dosed with the various statins for 30 days. The effect of statins on maximal electroshock and pentylenetetrazole induced seizures was then studied. The animals were then sacrificed and the brain tissue was used for antioxidant estimation. Results: Statins showed a protective effect against seizures in both the models. The levels of glutathione were increased and malonadialdehyde decreased in the brain tissue in statin treated groups. The present study confirms the anticonvulsant action of statins, their antioxidant action being the possible mechanism.

Keywords: statins, seizures , antioxidant action

Full Text:


Statins, the most widely used and efficacious  hypolipidemic which act by inhibiting HMG-CoA reductase enzyme are now known to have many pleotropic effects1 .The pleiotropic effects of statins include improving endothelial function, enhancing stability of plaques, decreasing oxidative stress, inflammation and inhibiting thrombosis1,2.

It has been hypothesized that statins reduce the risk of developing epilepsy in the elderly. 3 High dose atorvastatin has been shown to reduce the frequency of tonic-clonic seizures induced by quinolinic or kainic acid. 4 A cohort study also showed that statins reduced the hospitalization due to seizures3. Based on these studies, the authors had studied the effect of statins in animal models of epilepsy after a single dosing, wherein simvastatin had reduced the duration of seizures in maximum electroshock (MES) model without abolishing hindlimb extension. In pentylenetetrazole (PTZ) model simvastatin and lovastatin decreased the duration of seizures and also increased the latency for the onset of seizures in comparison to the control group. Atorvastatin at a dose of 3.6mg/kg increased the latency but had no effect on duration of seizures in PTZ model. 5 The results of the study indicated that statins do have an antiepileptic action but needed further confirmation.    Hence the authors planned to study the effect of chronic administration of various statins on MES and PTZ induced seizures and also their impact on oxidative changes which occur during seizures.


Albino rats weighing 150-200g were used for the study. They were maintained under standard conditions in Central animal house, Manipal University, Manipal approved by the CPCSEA.

The rats were kept in polypropylene cages (U.N. Shah Manufacturers, Mumbai) and maintained on standard pellet diet (Amrut Lab Animal Feed, Pranav Agro industries Ltd, Sangli, Maharashtra) and water ad libitum. The rats were maintained at a room temperature 26 ±20C, relative humidity 45?55% and light/ dark cycle of 12 h.

Reagents : Special chemicals such as 5 5’-dithio-bis (2-nitrobenzoic acid) (DTNB), 1-cholro 2, 4-dinitrobenzene (CDNB) ,reduced glutathione (GSH), thiobarbituric acid (TBA), trichloroacetic acid (TCA)  were obtained from Sigma Chemicals Co. (St Louis, MO). All the reagents used were of analytical grade

Drugs: Atorvastatin (Zydus Cadila Healthcare Ltd), simvastatin (Micro Labs Ltd), lovastatin (Dr.Reddy’s Laboratories Ltd), carbamazepine (Novartis India Ltd, Mumbai), sodium valproate (Sun Pharmaceutical Industries Ltd, Mumbai) and pentylenetetrazole (Sigma – Aldrich,

Mumbai) were used for the study. The doses selected were in accordance to that of the previous study done by the authors. 5   

Methodology:  The study was undertaken after obtaining permission from the Institutional Animal Ethics committee, Manipal. A total of sixty animals were used for the study. They were divided into two sets for testing in two experimental models, the maximal electroshock and pentylenetetrazole seizures.

I: Maximal electroshock model 

Rats were divided into 5 groups (n=6). The groups I to V received gum acacia (1ml), carbamazepine (108mg/kg), atorvastatin (7.2 mg/kg), simvastatin (1.80mg/kg) and lovastatin (3.60mg/kg ) respectively orally once daily for 30 days. Maximal electroshock seizures was induced as described by Toman et al6  with a current of 150 mA delivered through the ear clip electrode for 0.2 sec with the help of convulsiometer after a month of drug administration. Absence of hind limb extension (HLE) was taken as protection against seizures. Only the animals which show hind limb extension during the screening procedure on the earlier day were included in the study.

II: PTZ induced seizures7

 Rats were divided into 5  groups (n=6).The groups I to V received gum acacia (1ml),sodium valproate (180mg/kg), atorvastatin (7.2mg/kg), simvastatin (1.80mg/kg) and lovastatin (3.60mg/kg) respectively orally once daily for 30 days. Pentylenetetrazole (60mg/kg i.p) was then given to induce seizures after a month of drug administration. Each animal was then placed in an individual cage for observation lasting 30min. The duration of the seizures in each group was recorded.


Collection of tissue samples: The animals were sacrificed by cervical dislocation and brain tissues were carefully removed and chilled in ice-cold phosphate buffer. After washing in ice-cold buffer, the hippocampus was dissected out and homogenized in phosphate buffer (pH 7.4, 10% w/v) using Teflon homogenizer. The tissue homogenate was then utilized for

malondialdehyde (MDA) assay and glutathione-S- transferase (GST) assay.

Malondialdehyde assay Level of MDA was analyzed in the rat brain by the method of Okhawa et al with slight modifications8.100µL of homogenate, 1000µL of TBA and 500 µL of TCA were mixed and incubated at 100° for 20 minutes , then centrifuged at 12000 rpm for 5minutes . Absorbance was read spectrophotometrically at 532 nm.

Glutathione-S-transferase assay GST assay was analyzed in the rat brain by the method of Habig.9  Phosphate buffer (850µL),  CDNB (50 µL) and GSH (50 µL) were mixed and incubated at 37°C for ten minutes, then 50 µLof homogenate was added and absorbance was read spectrophotometrically at 340 nm.

Statistics: The results were analysed by one way ANOVA followed by Dunnett’s test. Statistical analysis was done using the SPSS 16.0 version.


In the present study, there was a significant (p≤ 0.05) reduction in the duration of PTZ induced seizures in atorvastatin, lovastatin, simvastatin and sodium valproate treated groups in comparison to the control group (62.93±3.43).  In maximal electroshock induced seizure model carbamazepine, atorvastatin, simvastatin and lovastatin significantly (< 0.01) reduced the duration of seizures in comparison to control group (Table1). The tissue glutathione levels were significantly (p<0.05) increased in the atorvastatin and simvastatin treated groups and malanodialdehyde levels were significantly (p<0.05) reduced by all the treated groups in comparison to control (Table 2). 


The present study demonstrates the anticonvulsant action of statins following chronic administration. In the previous study conducted by the authors, atorvastatin following a single dose had not shown antiseizure activity in both the models. Hence in the present study the dose of atorvastatin had been increased. The higher dose of atorvastatin reduced the duration of seizures both in the MES and PTZ models. Our findings are in accordance to the earlier study reports5. The protective effect of higher dose of atorvastatin against seizures can be attributed to its poor lipophilicity.

Neuronal hyper excitability and oxidative stress have been suggested to be responsible for various neurological diseases and epilepsy. Studies have shown that antioxidants can reduce seizure manifestations and the markers of oxidative stress 10. Oxidative stress is one of the etiological factors in inducing seizures in various epilepsy models. Drugs with antioxidant action have a potential as adjuvants to antiepileptic drugs. 11

Peroxidation of polyunsaturated fatty acids in cell membrane produces malonadialdehyde. The production of MDA is used as a marker to measure the level of oxidative damage in tissues. The nervous tissue is prone for damage by oxidative stress due to large amounts of polyunsaturated fatty acids which are susceptible for lipid peroxidation. Elevated levels of MDA in the brain issue have been detected in patients with epilepsy.12  In the present study atorvastatin , simvastatin and lovastatin significantly decreased the MDA levels  in the brain when compared to control group. Hence, the statins by virtue of their antioxidant action reduced the levels of elevated MDA produced due to oxidative stress.  

Cellular glutathione which is a major antioxidant is maintained by enzymes such as glutathione-s – transferase and glutathione reductase and the inhibition of activities of these enzymes therefore would deplete cellular reduced glutathione level and increase the accumulation of toxic metabolites [13]. In the present study the statins replenished the stores of glutathione which was depleted in the control group, suggesting their antioxidant action. Production of nitric oxide, 14 inhibition of neuroinflammation15 have also been suggested to be the possible mechanism by which statins can produce antiseizure activity.


In the present study, statins showed an anticonvulsant action. Antioxidant action of statins as the possible mechanism of their anticonvulsant action can also be hypothesized from this study. Further research and clinical trials are warranted to justify their use either alone or as adjuvants to antiepileptics in future.


We would like to acknowledge the guidance of the head of the department and Dean of Kasturba Medical College for proving the adequate infrastructure and reources required for the study


  1.  Bersot TP. Drug therapy for hypercholesterolemia and dyslipidemia. In: Brunton LL, Chabner BA, Knollmann BC, editors. Goodman and Gilman‘s The pharmacological basis of therapeutics .12thed. New  York: Mc Graw Hill ; 2006.p. 877-908.
  2. Zhou Q, Liao JK. Pleiotropic effects of statins. Circulation journal. 2010; 74: 818-826
  3. Das RR, Herman ST. Statins in epilepsy. Neurology 2010; 75: 1490-1491
  4. Lee JK Won JS, Singh AK, Singh I. Statin inhibits kainic acid-induced seizure and associated      inflammation and hippocampal cell death. Neurosci Lett 2008; 440(3):260-4.
  5. Nayak V, Adiga S, Poornima BM, Sharma R, Garg A. Effect of atorvastatin, simvastatin,lovastatin on animal models of epilepsy : a comparative study. International journal of current research and review 2012; 4(11):30-33.
  6. Toman JEP, Swinyard EA, Goodman LS. Properties of maximal seizures and their alteration by anticonvulsant drugs and other agents. J Neurophysiol 1946; 9:231-39.
  7. Visweswari G, Prasad KS, Chetan PS, Lokanatha V, Rajendra W. Evaluation of the anticonvulsant effect of Centella asiatica (gotu kola) in pentylenetetrazol-induced seizures with respect to cholinergic neurotransmission. Epilepsy and Behavior 2010; 17(3):332-335.
  8. Okhawa H, Ohishi N, Yagi K. Anal Biochem 1979; 95:351–358.
  9. Habig WH, Pabst MJ, Jakaby WB. Glutathione-S-transferase: the first enzymatic tep in mercapturic acid formation. J Biol Chem 1974;29: 7130-7139.
  10. Devi PU, Manocha A, Vohora D. Seizures, antiepileptics,antioxidantsand oxidative stress :an insight for researchers. Expert Opin Pharmacother 2008; 9(18):3169-77.
  11. Shin EJ, Jeong JH, Chung YH, Kim WK, Ko KH, Bach JH, et al. Role of oxidative stress in epileptic seizures. Neurochem Int 2011;59(2):122-37.
  12. Pandey MK, Mittra P, Maheshwari PK. The lipid peroxidation product as a marker of oxidative stress in epilepsy. JCDR 2012; 6(4): 590-92.
  13. Mueller SG, Trabesinger AH, Boesiger P, Wieser HG. Brain glutathione levels in patients with epilepsy measured by in vivo(1)H-MRS. Neurology 2001; 57(8): 1422-47.
  14. Moazzami K, Emamzadeh-Fard S, Shabani M. Anticonvulsive effect of atorvastatin on pentylenetetrazole induced seizures in mice: the role of nitric oxide pathway. Fundamental and clinical pharmacology 2013; 27:387-92.
  15. Mirhadi K. Anticonvulsant effect of pitavastatin in mice induced by pentylenetetrazole. American journal of animal and veterinary sciences 2011; 6(4):166-70.  

Research Incentive Schemes

Awards, Research and Publication incentive Schemes by IJCRR

Best Article Award: 

One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to for more details.

Women Researcher Award:

This award is instituted to encourage women researchers to publish her work in IJCRR. Women researcher, who intends to publish her research work in IJCRR as the first author is eligible to apply for this award. Editorial Board members decide on the selection of women researchers based on the originality, novelty, and social contribution of the research work. The corresponding author of the selected manuscript is communicated and information is displayed on IJCRR’s website. Under this award selected women, the author is eligible for publication incentives. Drop a mail to for more details.

Emerging Researcher Award:

‘Emerging Researcher Award’ is instituted to encourage student researchers to publish their work in IJCRR. Student researchers, who intend to publish their research or review work in IJCRR as the first author are eligible to apply for this award. Editorial Board members decide on the selection of student researchers for the said award based on originality, novelty, and social applicability of the research work. Under this award selected student researcher is eligible for publication incentives. Drop a mail to for more details.

Best Article Award

A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma COLAKOGLU entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by Arpita M. et al entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09
Late to bed everyday? You may die early, get depression
Egg a day tied to lower risk of heart disease
88 Percent Of Delhi Population Has Vitamin D Deficiency: ASSOCHAM Report

List of Awardees

Awardees of COVID-19 Research

Woman Researcher Award

A Study by Neha Garg et al. entitled "Optimization of the Response to nCOVID-19 Pandemic in Pregnant Women – An Urgent Appeal in Indian Scenario" published in Vol 12 issue 09

A Study by Sana Parveen and Shraddha Jain entitled "Pathophysiologic Enigma of COVID-19 Pandemic with Clinical Correlates" published in Vol 12 issue 13

A Study by Rashmi Jain et al. entitled "Current Consensus Review Article on Drugs and Biologics against nCOVID-19 – A Systematic Review" published in Vol 12 issue 09

Emerging Researcher Award

A Study by Madhan Jeyaraman et al. entitled "Vitamin-D: An Immune Shield Against nCOVID-19" published in Vol 12 issue 09

Study by Dheeraj Kumar Chopra et al. entitled "Lipid-Based Solid Dispersions of Azilsartan Medoxomil with Improved Oral Bioavailability: In Vitro and In Vivo Evaluation" published in Vol 12 issue 19

RSS feed

Indexed and Abstracted in

Antiplagiarism Policy: IJCRR strongly condemn and discourage practice of plagiarism. All received manuscripts have to pass through "Plagiarism Detection Software" test before forwarding for peer review. We consider "Plagiarism is a crime"

IJCRR Code of Conduct: We at IJCRR voluntarily adopt policies on Code of Conduct, and Code of Ethics given by OASPA and COPE. To know about IJCRRs Code of Conduct, Code of Ethics, Artical Retraction policy, Digital Preservation Policy, and Journals Licence policy click here

Disclaimer: International Journal of Current Research and Review (JICRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal.

Company name

International Journal of Current Research and Review (JICRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal


148, IMSR Building, Ayurvedic Layout,
        Near NIT Complex, Sakkardara,
        Nagpur-24, Maharashtra State, India

Copyright © 2020 IJCRR. Specialized online journals by ubijournal .Website by Ubitech solutions