Potential anti-seizure activity of atorvastatin in rat models of seizure

Authors

  • Ashwini P. Singh Department of Pharmacology, SDM College of Medical Sciences and Hospital, Dharwad, Karnataka, India
  • Radhika M. S. Department of Pharmacology, SDM College of Medical Sciences and Hospital, Dharwad, Karnataka, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20164506

Keywords:

Anticonvulsant, Atorvastatin, Maximal electroshock (MES), Pentylenetetrazole (PTZ), Phenytoin, Sodium valproate

Abstract

Background: Atorvastatin belongs to the class of Hypolipidemic statins. Increasing evidence indicates that statins are neuroprotective in several conditions, including stroke, cerebral ischemia and traumatic brain injury. However, only scanty and controversial reports are available on anticonvulsant action of statins. The present study therefore aims at exploring the influence of atorvastatin on seizures as compared to standard anticonvulsants phenytoin and sodium valproate in Wistar rats.

Methods: Rats were divided into 8 groups (n=6), each treated intraperitoneally (i.p) with atorvastatin, phenytoin or sodium valproate in their therapeutic equivalent doses. Their effects were evaluated on seizures induced by maximum electroshock seizure (MES) and pentylenetetrazole (PTZ). Hind limb extension (HLE) in MES model, number of seizures, duration of seizure, number of myoclonic jerks and time for onset as well as recovery from seizures in PTZ model were monitored. Statistical analysis was done using Kruskal-Wallis ANOVA and Mann-Whitney U test for significance.

Results: Atorvastatin failed to protect rats against HLE in MES seizure model. However, atorvastatin significantly prolonged seizure onset time (p<0.0547), decreased seizure number (p<0.0082), seizure duration (p<0.0547) and recovery time (p<0.0040) in PTZ model indicating its potential antiepileptic activity in PTZ model.

Conclusions: Atorvastatin exhibited protection against seizures only in PTZ seizure model. Hence, it could possess anti absence seizure activity. This needs to be established with further systematic animal and clinical studies.

References

Epilepsy. World Health Organisation, 2016. Available at: http://www.who.int/mediacentre/factsheets/fs999/en/. Accessed on 14 April 2016.

Devi PU, Manocha A, Vohora D. Seizures, antiepileptics, antioxidants and oxidative stress: an insight for researchers. Expert Opin Pharmacother. 2008;9(18):3169-77.

Shafaroodi H, Mezi L, Fakhrzad A, Hassanipour M, Rezayat M, Dehpour AR. The involvement of nitric oxide in the anti- seizure effect of acute Atorvastatin treatment in mice. Neurol Res. 2012;34(9):847-53.

Ramirez C, Tercero I, Pineda A, Burgos JS. Simvastatin is the statin that most efficiently protects against kinate-induced excitotoxicity and memory impairment. J. Alzheimers Dis. 2011;24(1):161-74.

Moezi L, Shafaroodi H, Hassanpuri M, Fakhrzad A, Hassanpour S, Dehpour AR. Chronic administration of atorvastatin induced anti-convulsant effects in mice: the role of nitric oxide. Epilepsy Behav. 2012;23(4):399-404.

Rajangam J, Manogna K, Mounica K, Padma C, Sawthi A. Behavioral influence of atorvastatin alone and in combination with antiepileptics against electroconvulsions in mice. Malays. J. Med. Biol. Res. 2015;2(3):224-30.

Kumar S, Megha M, Chogtu B, Bairy LK. Effects of acute and chronic administration of losartan, atorvastatin and their combination on animal models of epilepsy. Research journal of pharmaceutical, biological and chemical sciences. 2015;6(4):1795-801.

Nayak V, Adiga S, Poornima BM, Sharma R, Garg A, Shetty M. Effect of chronic administration of atorvastatin, simvastatin and lovastatin on animal model of epilepsy. International journal of current research and review. 2013;5(19):61-5.

Gupta YK, Malhotra J, George B, Kulkarni SK. Methods and considerations for experimental evaluation of antiepileptic drugs. Indian J Physiol Pharmacol. 1999;43(1):25-43.

Louis JW, Papanicolaou J, Summers JR, Vajda JF. Role of beta-adrenoreceptors in the control of pentanyltetrazol- induced convulsion in rats. Br J Pharmacol. 1982;75(3):441-6.

Moazzami K, Emamzadeh-Fard H, Shabani M. Anticonvulsant effect of atorvastatin on pentylenetetrazole-induced seizure in mice: the role of nitric oxide pathway. Fundam clin pharmacol. 2013;27(4):44-7.

Bosel J, Gandor F, Harms C, Synowitz M, Harms U, Djoufack PC, et al. Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones. J Neurochem. 2005;92(6):1386-98.

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Published

2016-12-24

How to Cite

Singh, A. P., & M. S., R. (2016). Potential anti-seizure activity of atorvastatin in rat models of seizure. International Journal of Basic & Clinical Pharmacology, 6(1), 35–38. https://doi.org/10.18203/2319-2003.ijbcp20164506

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Original Research Articles