:: Volume 22, Issue 3 (Bimonthly 2018) ::
Feyz Med Sci J 2018, 22(3): 258-266 Back to browse issues page
The effect of cyclooxygenase-2 inhibition on pentylenetetrazole-induced seizure threshold in mice
Azam Mesdaghinia , Paria Khazaee , Azhdar Heydari *
Physiology Research ‍Center, Kashan, University of Medical Sciences, Kashan, I. R. Iran. , heydariazh@gmail.com
Abstract:   (3459 Views)
Background: Previous studies have shown the protective effect of cyclooxygenase (COX) enzyme in development of convulsions. However, involvement of COX-2 in the pathogenesis of epilepsy is not yet well-known. The present study was designed to investigate the effect of celecoxib and nimesulide (selective COX-2 inhibitors) on pentylenetetrazole (PTZ)-induced clonic seizure threshold in mice.
Materials and Methods: In this study, white male mice were randomly divided into 13 groups including control groups, solvent (Tween 80) and eleven experimental groups which received celecoxib (2.5, 5 and 10 mg/kg), nimesulide (2.5, 5 and 10 mg/kg), diazepam (0.1, 0.5 and 5 mg/kg), and combination of non-effective dose of diazepam with celecoxib or nimesulide. Pentylenetetrazol-induced clonic seizure threshold was assessed in all groups.
Results: Nimesulide (2.5 and 5 mg/kg), celecoxib (2.5 and 5 mg/kg), and diazepam (0.5 and 5 mg/kg) significantly increased the PTZ-induced seizure threshold compared with the solvent group (P<0.05). Also, only combination of sub-effective dose of diazepam (0.1 mg/kg) with celecoxib (2.5 mg/kg) showed a significant protective effect against PTZ-induced seizure threshold (P<0.01).
Conclusion: Findings of the current study show the possible role of COX-2 isoenzyme in the pathophysiology of epilepsy. It is possible that some COX-2 inhibitors such as celecoxib act through GABAergic neurons and reduce excitability by increasing GABA release. Also, the difference between the effects of celecoxib and nimesulide can be attributed to the effect of these two compounds on COX-1 and COX-2 expression.
Keywords: Seizure, Pentylenetetrazole, Cyclooxygenase-2, GABA
Full-Text [PDF 186 kb]   (894 Downloads)    
Type of Study: Research | Subject: General
Received: 2018/05/8 | Revised: 2018/08/5 | Accepted: 2018/06/17 | Published: 2018/08/4
References
1. Stafstrom CE, Carmant L. Seizures and epi‌le‌psy: an overview for neuroscientists. Cold Spring Harb Perspect Med 2015; 5(6).
2. Rojas A, Jiang J, Ganesh T, Yang MS, Lelutiu N, Gueorguieva P, et al. Cyclooxygenase-2 in epilepsy. Epilepsia 2014; 55(1): 17-25.
3. Katyal J, Kumar H, Gupta YK. Anticonvulsant activity of the cyclooxygenase-2 (COX-2) inhibitor etoricoxib in pentylenetetrazole-kindled rats is asso‌ciated with memory impairment. Epilepsy Behav 2015; 44: 98-103.
4. Tanaka S, Nakamura T, Sumitani K, Takahashi F, Konishi R, Itano T, et al. Stage- and region-specific cyclooxygenase expression and effects of a selective COX-1 inhibitor in the mouse amygdala kindling model. Neurosci Res 2009; 65(1): 79-87.
5. Suemaru K, Yoshikawa M, Tanaka A, Araki H, Aso H, Watanabe M. Anticonvulsant effects of ace-taminophen in mice: Comparison with the effects of nonsteroidal anti-inflammatory drugs. Epilepsy Res 2018; 140: 22-28.
6. Salvadori MG, Banderó CR, Jesse AC, Gomes AT, Rambo LM, Bueno LM, et al. Prostaglandin E(2) potentiates methylmalonate-induced seizures. Epilepsia 2012; 53(1): 189-98.
7. 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 (8): 1478–85.
8. Oliveira MS, Furian AF, Royes LF, Fighera MR, Fiorenza NG, Castelli M, et al. Cyclo‌oxy‌ge‌nase-2/PGE2 pathway facilitates pentylene‌tetra‌zol-induced seizures. Epilepsy Res 2008; 79(1): 14–21.
9. Claycomb RJ, Hewett SJ, Hewett JA. Prophy‌lactic, prandial rofecoxib treatment lacks efficacy against acute PTZ-induced seizure generation and kindling acquisition. Epilepsia 2011; 52(2): 273–83.
10. Gobbo OL, O'Mara SM. Post-treatment, but not pre-treatment, with the selective cyclo‌oxy‌genase-2 inhibitor celecoxib markedly enhances fun‌ctional recovery from kainic acid-induced neurodegeneration. Neuroscience 2004; 125(2): 317–27.
11. Serrano GE, Lelutiu N, Rojas A, Cochi S, Shaw R, Makinson CD, et al. Ablation of cyclo‌oxygenase-2 in forebrain neurons is neuroprotective and dampens brain inflammation after status epile‌pticus. J Neurosci 2011; 31(42): 14850-60.
12. Chen C, Bazan NG. Endogenous PGE2 regu‌lates membrane excitability and synaptic trans‌mission in hippocampal CA1 pyramidal neurons. J Neurophysiol 2005; 93(2): 929-41.
13. Heydari A, Davoudi S. The effect of sertraline and 8-OH-DPAT on the PTZ_induced seizure threshold: Role of the nitrergic system. Seizure 2017; 45: 119-24.
14. Mesdaghinia A, Yazdanpanah H, Seddighi M, Banafshe HR, Heydari A. Effect of short-term lead exposure on PTZ-induced seizure threshold in mice. Toxicol Lett 2010; 199(1): 6-9.
15. Yang H, Chen C. Cyclooxygenase-2 in syn‌a‌ptic signaling. Curr Pharm Des 2008; 14 (14): 1443–51.
16. Marcheselli VL, Bazan NG. Sustained induc-tion of prostaglandin endoperoxide synthase-2by seizures in hippocampus. J Biol Chem 1996; 271 (40): 24794–9.
17. Desjardins P, Sauvageau A, Bouthillier A, Navarro D, Hazell AS, Rose C, et al. Induction of astrocytic cyclooxygenase-2 in epileptic patients with hippocampal sclerosis. Neurochem Int 2003; 42 (4): 299-303.
18. Okada K. Yuhi T. Tsuji S. Yamashita U. Cyclo‌oxygenase-2 expression in the hippocampus of genetically epilepsy suscepti-ble El mice were increased after seizure. Brain Res 2001; 894 (2): 332-5.
19. Akarsu ES, Ozdayi S, Algan E, Ulupinar F. The neuronal excitability time-dependently changes fter lipopolysaccharide administration in mice: possible role of cyclooxygenase-2 induction. Epi‌lepsy Res 2006; 71(2-3): 181-7.
20. Ciceri P, Zhang Y, Shaffer AF, Leahy KM, Woerner MB, Smith WG, et al. Pharmacology of celecoxib in rat brain after kainate administration. J Pharmacol Exp Ther 2002; 302(3): 846-852.
21. Ueno N, Takegoshi Y, Kamei D, Kudo I. Murakami M. Coupling between cyclooxygenases and terminal prostanoid synthases. Biochem Biophys Res Commun 2005; 338(1): 70-6.
22. Rowley NM, Madsen KK, Schousboe A, Steve White H. Glutamate and GABA synthesis, release, transport and metabolism as targets for seizure control. Neurochem Int 2012; 61(4): 546-58.
23. Olsen RW. GABAA receptor: Positive and negativeallosteric modulators. Neuropharmacology 2018; S0028-3908(18): 30036-4.
24. Dhir A, Naidu PS, Kulkarni SK. Neuro‌protective effect of nimesulide, a preferential COX-2 inhibitor, against pentylenetetrazol (PTZ)-induced chemical kindling and associated bio‌chemical parameters in mice. Seizure 2007; 16(8): 691-7.
25. Liu B, Luo W, Zhang Y, Li H, Zhu N, Huang D, Zhou Y. Effect of celecoxib on cyclooxygenase-1-mediated prostacyclin synthesis and endothelium-dependent contraction in mouse arteries. Eur J Pharmacol 2013; 698(1-3): 354-61.
26. Sang N, Zhang J, Chen C. COX-2 oxidative metabolite of endocannabinoid 2-AG enhances excitatory glutamatergic synaptic transmission and induces neurotoxicity. J Neurochem 2007; 102(6): 1966-77.
27. Andrade C, Singh NM, Thyagarajan S, Naga‌raja N, Sanjay Kumar Rao N, et al. Possible gluta‌matergic and lipid signalling mechanisms in ECT-induced retrograde amnesia: experimental evidence for involvement of COX-2, and review of literature. J Psychiatr Res 2008; 42(10): 837-50.

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