Author(s):
Sangita G. Kamath, Rajani Patil, Umakant Patil
Email(s):
sangita.kamath@manipal.edu
DOI:
10.52711/0974-360X.2023.00842 
Address:
Sangita G. Kamath1*, Rajani Patil2, Umakant Patil3
1Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India - 576104.
3Department of Pharmacology, Gadag Institute of Medical Sciences, Gadag, Karnataka, India - 582103.
4 Basaveshwara Medical College and Hospital, Chitradurga, Karnataka, India-577502.
*Corresponding Author
Published In:
Volume - 16,
Issue - 11,
Year - 2023
ABSTRACT:
Epilepsy is a common neurological condition a?ecting people of all ages and both sexes. Most of the currently used antiepileptic drugs have neurotoxic and teratogenic effects. There are scanty reports of anticonvulsant activity with statins. The present study was undertaken to evaluate the anticonvulsant effect of simvastatin using MES and PTZ models in mice and compare it with the standard drugs phenytoin and diazepam respectively.64 albino mice of either sex weighing 25-35g were divided into 8 groups of 8 mice each – 4 group each for MES and PTZ model. In MES model, seizures were induced via trans auricular electrodes with a current of 80mA for 0.2 second. Each mouse was pretreated with drugs 30 minutes before in both models. The different groups 1 to 4 were administered polyethylene glycol (0.5ml/Kg), phenytoin (20mg/kg), simvastatin (10mg/Kg) and simvastatin (20mg/Kg) respectively. In PTZ model, seizures were induced by giving PTZ 80mg/Kg. The different groups 5 to 8 were administered polyethylene glycol (0.5ml/Kg), diazepam (2mg/kg), simvastatin (10mg/Kg) and simvastatin (20mg/Kg) respectively. Statistical analysis was doneby ANOVA followed by Tukey’s post hoc analysis for group wise comparison. Results indicated that the anticonvulsant effect of simvastatin (10 and 20mg/Kg) was comparable to phenytoin in the MES model. In the PTZ model, simvastatin (10mg/Kg) produced a reduction in seizure duration but did not provide seizure protection as compared to that of the diazepam. The present study demonstrated the anticonvulsant effect of simvastatin. Further studies may explore the potential of this as an add-on drug in patients with dyslipidemia and epilepsy.
Cite this article:
Sangita G. Kamath, Rajani Patil, Umakant Patil. Study of Anticonvulsant effect of Simvastatin in Maximal Electroshock and Pentylenetetrazole Induced Seizure Model In Albino Mice. Research Journal of Pharmacy and Technology. 2023; 16(11):5193-7. doi: 10.52711/0974-360X.2023.00842
Cite(Electronic):
Sangita G. Kamath, Rajani Patil, Umakant Patil. Study of Anticonvulsant effect of Simvastatin in Maximal Electroshock and Pentylenetetrazole Induced Seizure Model In Albino Mice. Research Journal of Pharmacy and Technology. 2023; 16(11):5193-7. doi: 10.52711/0974-360X.2023.00842 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2023-16-11-36
REFERENCES:
1. Rogawski MA. Antiseizure Drugs. In Basic and clinical pharmacology, Edited by Katzung BG and Todd W V. McGraw Hill, New York. 2022; 15th ed: pp.1–41.
2. Seizures and epilepsy. In Harrisson’s Principles of Internal Medicine Vol - 2,Edited by Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J.McGraw Hill, New York. 2012; 18th ed: pp. 3251–69.
3. Eadie MJ. Sir Charles Locock and potassium bromide. The Journal of the Royal College of Physicians of Edinburg. 2012; 42: 274–9. DOI: 10.4997/JRCPE.2012.317
4. Ramirez C, Tercero I, Pineda A, Burgos JS. Simvastatin is the statin that most efficiently protects against kainate-induced excitotoxicity and memory impairment. Jounalof Alzheimer's Disease. 2011; 24(1): 161–74.DOI: 10.3233/JAD-2010-101653
5. Shankaran M, King C, Lee J, Busch R, Wolff M, Hellerstein MK. Discovery of Novel Hippocampal Neurogenic Agents by Using an in Vivo Stable Isotope Labeling Technique. Journal of Pharmacology and Experimental Therapeutics. 2006; 319(3): 1172–81. DOI: 10.1124/jpet.106.110510
6. Vijayalakshmi A, Ravichandiran V, Anbu J, Velraj M, Jayakumari S. Anticonvulsant and neurotoxicity profile of the rhizome of Smilax china Linn. in mice. Indian Journal of Pharmacology. 2011;43(1):27–30.doi: 10.4103/0253-7613.75662
7. Akula KK, Dhir A, Kulkarni SK. Effect of various antiepileptic drugs in a pentylenetetrazol-induced seizure model in mice. Methods and Findings in Experimental & Clinical Pharmacology. 2009; 31(7): 423–32. doi: 10.1358/mf.2009.31.7.1393610
8. Gupta SK. Drug screening methods. Jaypee Brothers medical Publishers (P) Ltd, New Delhi. 2004.
9. Laurence D, Bacharach A. Evaluation of drug activities : Pharmacometrics. Academia Press, London. 1964.
10. Inan S, Buyukafsar K. Antiepileptic effects of two Rho-kinase inhibitors, Y-27632 and fasudil, in mice. British Journalof Pharmacology. 2008; 155(1):44–51. doi: 10.1038/bjp.2008.225
11. Bum EN, Nkantchoua GN, Njikam N, Taiwe GS, Ngoupaye GT, Pelanken MM, et al. Anticonvulsant and sedative activity of leaves of Senna spectabilis in mice. International Journal of Pharmacology. 2010; 6(2): 123–8. DOI: 10.3923/ijp.2010.123.128
12. Nagakannan P, Shivsharan BD, Boreddy S Thippeswamy. Sedative and antiepileptic effects of Anthocephalus cadamba Roxb. Indian Journal of Pharmacology. 2011; 43(6): 699–702. doi: 10.4103/0253-7613.89829
13. De Sarro A, Cecchetti V, Fravolini V, Naccari F, Tabarrini O, De Sarro G. Effects of Novel 6-Desfluoroquinolones and Classic Quinolones on Pentylenetetrazole-Induced Seizures in Mice. Antimicrobial Agents and Chemotherapy. 1999; 43(7): 1729–36. doi: 10.1128/aac.43.7.1729
14. Ponce J, De La Ossa NP, Hurtado O, Millan M, Arenillas JF, Dávalos A, et al. Simvastatin reduces the association of NMDA receptors to lipid rafts: A cholesterol-mediated effect in neuroprotection. Stroke. 2008; 39(4): 1269–75. DOI: 10.1161/STROKEAHA.107.498923
15. Zacco A, Togo J, Spence K, Ellis A, Lloy D, Furlong S et al. 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Protect Cortical Neurons from Excitotoxicity. Journal of Neuroscience. 2003; 23(35): 11104–11. doi: 10.1523/JNEUROSCI.23-35-11104.2003
16. Citraro R, Chimirri S, Aiello R, Gallelli L, Trimboli F, Britti D et al. Protective effects of some statins on epileptogenesis and depressive‐like behavior in WAG/Rij rats, a genetic model of absence epilepsy. Epilepsia. 2014; 55(8):1284-91.doi: 10.1111/epi.12686
17. Johnson-anuna LN, Eckert GP, Keller JH, Igbavboa U, Franke C, Fechner T, et al. Chronic Administration of Statins Alters Multiple Gene Expression Patterns in Mouse Cerebral Cortex. The Journal of Pharmacology and Experimental Therapeutics. 2005; 12(2):786–93. doi: 10.1124/jpet.104.075028.
18. Sierra S, Ramos MC, Molina P, Esteo C, Vazquez JA, Burgos JS. Statins as neuroprotectants: a comparative in vitro study of lipophilicity, blood-brain-barrier penetration, lowering of brain cholesterol, and decrease of neuron cell death. Journal of Alzheimer's Disease. 2011; 23(2): 307–18.doi: 10.3233/JAD-2010-101179
19. Hynd MR, Scott HL, Dodd PR. Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer’s disease. Neurochemistry International. 2004: 5(5): 583-95.doi: 10.1016/j.neuint.2004.03.007.
20. Rangel P, Cysneiros RM, Arida RM, Albuquerque MD, Colugnati DB, Scorza CA et al. Lovastatin Reduces Neuronal Cell Death In Hippocampal Ca1 Subfield After Pilocarpine-Induced Status Epilepticus Preliminary results. Arquivos de Neuro-Psiquiatria. 2005; 3(4): 972-6. doi: 10.1590/s0004-282x2005000600013
21. Franzoni F, Galvan AQ, Regoli F, Ferrannini E, Galetta F. A comparative study of the in vitro antioxidant activity of statins. Interntional Journalof Cardiology. 2003; 90(2-3):317-21. doi: 10.1016/s0167-5273(02)00577-6.
22. Mirhadi K. Anticonvulsant Effect of Pitavastatin in Mice Induced by Pentylenetetrazole. American Jounral of Animal and Veterninary Sciences.2011; 6(4): 166–70. DOI: https://doi.org/10.3844/ajavsp.2011.166.170
23. Tian GF, Azmi H, Takano T, Xu Q, Peng W, Lin J et al. An astrocytic basis of epilepsy. Nature Medicine. 2005; 11(9): 973-81.doi: 10.1038/nm1277.
24. Muramatsu Y, Kurosaki R, Kato H, Araki T. Effect of pitavastatin against expression of S100β protein in the gerbil hippocampus after transient cerebral ischaemia. Acta Physiologica. 2004; 82(1): 95-107.doi: 10.1111/j.1365-201X.2004.01300.x.
25. Quintana-Pájaro LDL, Ramos-Villegas Y, Cortecero-Sabalza E, Joaquim AF, Agrawal A, Narvaez-Rojas AR, et al. The effect of statins in epilepsy: A systematic review. Journal of Neurosciences in Rural Practice. 2018; 9(4): 478-86. doi: 10.4103/jnrp.jnrp_110_18.
26. Hsieh PF, Tung H, Lin CH. Statin effects on post-stroke epilepsy and mortality–Taiwan population-based study. Neurological Research. 2020; 42(5): 422-29. doi: 10.1080/01616412.2020.1735821.
27. Fang J, Tuo M, Ouyang K, Xu Y. Statin on post-stroke epilepsy: A systematic review and meta-analysis. J Clinical Neuroscience. 2021; 83: 83-87. doi: 10.1016/j.jocn.2020.11.023.
28. Nucera B, Rinaldi F, Nardone R, Lattanzi S, Brigo F. Statins in primary prevention of poststroke seizures and epilepsy: A systematic review. Epilepsy and Behaviour. 2020; 12: 107400. doi: 10.1016/j.yebeh.2020.107400.
29. Klein P, Friedman A, Hameed MQ, Kaminski RM, Bar-Klein G, Klitgaard H, et al. Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy? Epilepsia. 2020; 1(3): 359-86. doi: 10.1111/epi.16450.