Evaluation of anticonvulsant effect of celecoxib, a selective cyclooxygenase-2 inhibitor in experimentally induced convulsions in albino rats
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20162454Keywords:
Cycloxygenase-2, Celecoxib, MES test, Pentylenetetrazole testAbstract
Background: Cyclooxygenase-2 (COX-2) exists as the inducible form of the cyclooxygenase enzyme, the levels of which are elevated in inflammatory conditions. COX-2 is located in regions of brain like hippocampus and cerebral cortex. When induced, COX-2 forms prostaglandin E2 (PGE2), which is responsible for CNS excitation, in turn leading to generation of seizures. COX-2 inhibitors by preventing the formation of PGE2 may serve as effective anticonvulsants. Since none of the anti-epileptics in current use are able to cure the patient of the seizures, a search for newer anti-epileptics is warranted. The present study assesses the anti-seizure activity of celecoxib against experimentally induced convulsions in Albino rats.
Methods: Two models of experimentally induced convulsions in Albino rats were used: 1) maximum electroshock seizure (MES) test model and 2) pentylenetetrazole (PTZ) test model. 30 rats were taken for each method and randomly assigned to 5 groups (N=6). 1st group served as control group, which received normal saline intra-peritoneal. 2nd, 3rd and 4th groups received celecoxib in doses of 10, 20 and 40 mg respectively through intraperitoneal route. The 5th group received the standard drugs phenytoin sodium (12.5 mg/kg) and sodium valproate (100 mg/kg) through intraperitoneal route in MES and PTZ models respectively.
Results: Celecoxib showed significant anticonvulsant effect with all 3 doses in MES model and with 2 doses (20 and 40 mg/kg) with PTZ model.
Conclusions: The results of this study indicate that celecoxib has anticonvulsant effect in albino rats.
References
Epilepsy. World Health Organization. 2016. Available at http://www.who.int/mediacentre/factsheets/fs999/en/. Accessed on 15 April 2016.
Loscher W. Current status and future directions in the pharmacotherapy of epilepsy. Trends Pharmacol Sci. 2002;23(3):113-8.
Haris RH, Ramwell PW. Cellular mechanism of prostaglandin action. Ann Rev Physiol. 1979;41:653.
Minghetti L, Pocchiari M. Cyclooxygenase-2, prostaglandin E2 and microglial activation in prion diseases. International Review of Neurobiology. 2007;82:265-75.
Takemiya T, Suzuki K, Sugiura H, Yasuda S, Yamagata K, Kawakami Y, et al. Inducible brain COX-2 facilitates the recurrence of hippocampal seizures in mouse rapid kindling. Prostaglandins and Other Lipid Medi. 2003;71:205-16.
Shimada T, Takemiya T, Sugiura H, Yamagata K. Role of inflammatory mediators in the pathogenesis of epilepsy. Mediators of Inflammation. 2014;2014:1-8.
White HS. Preclinical development of antiepileptic drugs: past, present, and future directions. Epilepsia. 2003;44(7):2-8.
Castel-Branco MM, Alves GL, Figueiredo IV, Falcão AC, Caramona MM. The maximal electroshock seizure (MES) model in the preclinical assessment of potential new antiepileptic drugs. Methods Find Exp Clin Pharmacol. 2009;31(2):101-6.
Holmes G. Animal model studies application to human patients. Neurology. 2007;69(24):S28-S32.
Srivastava AK, Gupta YK. Aspirin modulates the anticonvulsant effect of diazepam and sodium valproate in pentylenetetrazole and maximal electroshock induced seizures in mice. Indian J Physiol Pharmacol. 2001;45:475-80.
Dhir A, Naidu PS, Kulkarni SK. Effect of cyclooxygenase inhibitors on pentylenetetrazol (PTZ)-induced convulsions: possible mechanism of action. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:1478-85.
Yang H, Chen C. Cyclooxygenase-2 in synaptic signaling. Curr Pharm Des. 2008;14:1443-51.
Oliveira MS, Furian AF, Rambo LM, Ribeiro LR, Royes LF, Ferreira J, et al. Modulation of pentylenetetrazol-induced seizures by prostaglandin E2 receptors. Neuroscience. 2008;152(4):1110-8.
Choi SH, Aid S, Bosetti F. The distinct roles of cyclooxygenase-1 and -2 in neuroinflammation: implications for translational research. Trends Pharmacol Sci. 2009;30:174-81.
Yang H, Chen C. Cyclooxygenase-2 in synaptic signaling. Curr Pharm Des. 2008;14:1443-51.
Jiang JY, Ganesh QT, Puolit WA, Dudek FE, Dingledine R. Inhibition of the prostaglandin receptor EP2 following status epilepticus reduces delayed mortality and brain inflammation. Proc Natl Acad Sci USA. 2013;110:3591-6.
Takemiya T, Yamagata K. Intercellular signaling pathway among endothelia, astrocytes and neurons in excitatory neuronal damage. Int J Mol Sci. 2013;14:8345-57.
Chen C, Bazan NG. Endogenous PGE2 regulates membrane excitability and synaptic transmission in hippocampal CA1 pyramidal neurons. J Neurophysiol. 2005;93:929-41.
Mirjany M, Ho L, Pasinetti G. Role of cyclooxygenase-2 in neuronal cell cycle activity and glutamate-mediated excitotoxicity. J Pharmacol Exp Ther. 2002;301(2):494-500.
Takadera T, Shiraishi Y, Ohyashiki T. Prostaglandin E2 induced caspase-dependent apoptosis possibly through activation of EP2 receptors in cultured hippocampal neurons. Neurochem Int. 2004;45(5):713-9.
Takemiya T, Suzuki K, Sugiura H, Yasuda S, Yamagata K, Kawakami Y, et al. Inducible brain COX-2 facilitates the recurrence of hippocampal seizures in mouse rapid kindling. Prostagland Other Lipid Meadiators. 2003;71:205.
Shafiq N, Malhotra S, Pandhi P. Anticonvulsant action of celecoxib (alone and in combination with sub-threshold dose of phenytoin) in electroshock induced convulsion. Method Find Ex. Clin Pharmacol. 2003;25(2):87-90.
Dhir A, Kulkarni SK. Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor potentiates the anticonvulsant activity of tiagabine against pentylenetetrazol-induced convulsions in mice. Inflammopharmacology. 2006;14:222-5.
Akarsu ES, Ozdayi S, Algan E, Ulupinar F. The neuronal excitability time-dependently changes after lipopolysaccharide administration in mice: possible role of cyclooxygenase-2 induction. Epilepsy Res. 2006;71:181-7.
Bhaduri J, Hota D, Acharya SB. Role of prostaglandin synthesis inhibitors on chemically induced seizures. Indian J Exp Biol. 1995;33:677-81.
