TY - JOUR T1 - The Role of Captopril on Pentylenetetrazole-Induced Seizures in Rats AU - Çetindağ Çiltaş, Arzuhan AU - Şahin, Bilal PY - 2023 DA - September Y2 - 2023 DO - 10.51972/tfsd.1333472 JF - Turkish Journal of Science and Health JO - TFSD PB - Ümit Muhammet KOÇYİĞİT WT - DergiPark SN - 2717-7173 SP - 240 EP - 247 VL - 4 IS - 3 LA - en AB - ABSTRACT: Purpose: In recent years, experimental studies have shown that some angiotensin-converting enzyme (ACE) inhibitors with antihypertensive effects have anticonvulsant effects against seizures. After the seizure, the process of inflammation begins in the brain and body, with the production of free radicals. Renin has some effects on the central nervous system of the angiotensin system. The current study's objective was to examine how captopril, an ACE inhibitor, affects neuroinflammation in the hippocampus and cortical areas in acute epileptic seizures and post-seizures induced by pentylenetetrazole (PTZ).Material and Methods: Eighteen Wistar Albino rats were separated into three groups: control, PTZ (serum physiologic 1 ml/kg as solvent), and captopril (50 mg/kg/day for 7days). To produce epileptic seizures, PTZ (45 mg/kg) was delivered thirty minutes after the drug was administered. The animals were monitored during 30 minutes to record seizures scoring scale and the onset time of first myoclonic jerk (FMJ). In the brain tissue, the activity of TNF- α, IL-1 β, NF-kB, COX-1, and COX-2 were examined.Results: Captopril increased FMJ onset time and reduced seizure stage as compared to the PTZ group (p KW - Captopril KW - Epilepsy KW - Pentylenetetrazole KW - Neuroinflammation KW - Rat CR - Abareshi, A., Hosseini, M., Beheshti, F., et al. (2016). The effects of captopril on lipopolysaccharide induced learning and memory impairments and the brain cytokine levels and oxidative damage in rats. Life Sci, 167, 46-5. https://doi.org/10.1016/j.lfs.2016.10.026 CR - Abbassi, Y.A., Mohammadi, M.T., Foroshani, M.S., et al. (2016). Captopril and valsartan may improve cognitive function through potentiation of the brain antioxidant defense system and attenuation of oxidative/nitrosative damage in STZ-induced dementia in rat. Adv Pharm Bul, 6(4), 531-539. doi:10.15171/apb.2016.067 CR - Abraham, J., Fox, P.D., Condello, C., et al. (2012). Minocycline attenuates microglia activation and blocks the long-term epileptogenic effects of early-life seizures. Neurobiol Dis, 46(2), 425-430. https://doi.org/10.1016/j.nbd.2012.02.006 CR - Asgharzadeh, F., Hosseini, M., Bargi, R., et al. (2019). Effect of Captopril on Brain Oxidative Damage in PentylenetetrazoleInduced Seizures in Mice. Pharmaceutical Sciences, 25 (3), 221-226. doi: 10.15171/PS.2019.38 CR - Bild, W., Hritcu, L., Stefanescu, C., et al. (2012). Inhibition of central angiotensin II enhances memory function and reduces oxidative stress status in rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry, 243, 79-88. https://doi.org/10.1016/j.pnpbp.2012.12.009 CR - Braszko, J.J., Karwowska-Polecka, W., Halicka, D., et al (2003). Captopril And Enalapril Improve Cognition And Depressed Mood In Hypertensive Patients. J Basic Clin Physiol Pharmacol, 14(4), 323-43. https://doi.org/10.1515/JBCPP.2003.14.4.323 CR - Campolo, M., Casili, G., Biundo, F., et al (2017). The Neuroprotective Effect of Dimethyl Fumarate in an MPTP-Mouse Model of Parkinson's Disease: Involvement of Reactive Oxygen Species/Nuclear Factor-κB/Nuclear Transcription Factor Related to NFE2: Antioxid Redox Signal, 27(8), 453-471. https://doi.org/10.1089/ars.2016.6800 CR - Cernak, I., O'Connor, C., Vink, R. (2011). Activation Of Cyclo-Oxygenase-2 Contributes To Motor And Cognitive Dysfunction Following Diffuse Traumatic Brain Injury In Rats. Clin Exp Pharmacol Physiol, 28(11), 22-25. https://doi.org/10.1046/j.1440-1681.2001.03549.x CR - Chen, Z., Brodie, M.J., Liew, D., et al (2018). Treatment Outcomes in Patients with Newly Diagnosed Epilepsy Treated with Established and New Antiepileptic Drugs: A 30-Year Longitudinal Cohort Study. JAMA Neuro, 75(3), 279-286. doi:10.1001/jamaneurol.2017.3949 CR - Ciltas, A.C., Toy, C.E., Güneş, H., et al (2023). Effects ofprobiotics on GABA/glutamate and oxidative stress in PTZ- induced acute seizure model in rats. Epilepsy Research, 195. https://doi.org/10.1016/j.eplepsyres.2023.107190 CR - Ciobica, A., Hritcu, L., Nastasa, V., et al (2011). Inhibition of central angiotensin converting enzyme exerts anxiolytic effects by decreasing brain oxidative stress. J Med Biochem, 30(2), 109-14. doi: 10.2478/v10011- 011-0009-3 CR - de Cavanagh, EM., Inserra, F., Ferder, L., et al (2000). Enalapril and captopril enhance glutathionedependent antioxidant defenses in Mouse tissues. Am J Physiol Regul Integr Comp Physiol, 278(3), 572-7. https://doi.org/10.1152/ajpregu.1997.272.2.R514 CR - De Luca, G., Di Giorgio, R.M., Macaione, S., et al (2004). Susceptibility to audiogenic seizure and neurotransmitter amino acid levels in different brain areas of IL-6-deficient mice. Pharmacol Biochem Behav, 78(1), 75-81. https://doi.org/10.1016/j.pbb.2004.02.004 CR - Desjardins, P., Sauvageau, A., Bouthillier, A., et al (2003). Induction of astrocytic cyclooxygenase-2 in epileptic patients with hippocampal sclerosis. Neurochem Int, 42(4), 299-303. https://doi.org/10.1016/S0197- 0186(02)00101-8 CR - Dhir, A., Naidu, P.S., Kulkarni, S.K. (2007). Neuroprotective effect of nimesulide, a preferential COX-2 inhibitor, against pentylenetetrazol (PTZ)-induced chemical kindling and associated biochemical parameters in mice. Seizure, 16(8), 691-697. https://doi.org/10.1016/j.seizure.2007.05.016 CR - Dingledine, R., Varvel, N.H., Dudek, F.E. (2014). When and how do seizures kill neurons, and is cell death relevant to epileptogenesis?. Adv Exp Med Biol, 813, 109-122. https://doi.org/10.1007/978-94-017-8914-1_9 CR - Erdogan, M.A., Yusuf, D., Erdogan, A., et al. (2019). Levodropropizine suppresses seizure activity in rats with pentylenetetrazol-induced epilepsy. Epilepsy Res, 150, 32-37. https://doi.org/10.1016/j.eplepsyres.2018.12.011 CR - Ernst, O., & Zor, T. (2010). Linearization of the Bradford protein assay. J Vis Exp. doi: 10.3791/1918 CR - Glass, C.K., Saijo, K., Winner, B., et al. (2010). Mechanisms underlying inflammation in neurodegeneration. Cell, 140(6), 918-934. https://doi.org/10.1016/j.cell.2010.02.016 CR - Gurer, H., Neal, R., Yang, P., et al. (1999). Captopril as an antioxidant in lead-exposed Fischer 344 rats. Hum Exp Toxicol, (1), 27-32. https://doi.org/10.1177/0960327199018001 CR - Ha, H., & Kim, KH. (1992). Amelioration of diabetic microalbuminuria and lipid peroxidation by captopril. Yonsei Med J, 33(3), 217-223 CR - Johnston, C. (1990). Biochemistry and Pharmacology of the Renin-Angiotensin System. Drugs, (39), 21-31. CR - Kandratavicius, L., Balista, P.A., Lopes-Aguiar, C., et al (2014). Animal models of epilepsy: use and limitations. Neuropsychiatr Dis Treat, 10,1693-1705. CR - Karabulut, S., & Taşkıran, A.Ş. (2021). Effect of Pre- Treatment with Acetaminophen on Hippocampal Oxidative, Inflammatory, and Apoptotic Parameters in PTZ-Induced Acute Seizure Mice Model. Neurochemical Journal, 5(1), 79-85. https://doi.org/10.1134/S1819712421010050 CR - Karimani, A., Mamashkhani, Y., Jafari, M., et al. (2018). Captopril attenuates diazinoninduced oxidative stress: a subchronic study in rats. Iran J Med Sci, 43(5), 514- 22. doı: 10.2147/NDT.S50371 CR - Kruger, NJ. (1994). The Bradford method for protein quantitation. Methods Mol Biol, 32, 9-15. CR - Mansoor, S.R., Hashemian, M., Khalili-Fomeshi, M., et al. (2018). Upregulation of klotho and erythropoietin contributes to the neuroprotection induced by curcumin-loaded nanoparticles in experimental model of chronic epilepsy. Brain Res Bull, 142, 281-288. https://doi.org/10.1016/j.brainresbull.2018.08.010 CR - Meili-Butz, S., Niermann, T., Fasler-Kan, E., et al. (2008). Dimethyl fumarate, a small molecule drug for psoriasis, inhibits Nuclear Factor-kappaB and reduces myocardial infarct size in rats. Eur J Pharmacol, 586(1- 3), 251-258. https://doi.org/10.1016/j.ejphar.2008.02.038 CR - Mowry, FE., & Biancardi, V.C. (2019). Neuroinflammation in hypertension. The renin-angiotensin system versus pro-resolution pathways. Pharmacol Res, 144, 279-91. https://doi.org/10.1016/j.phrs.2019.04.029 CR - Pitkänen, A., Lukasiuk, K., Dudek, F.E., et al. (2015). Epileptogenesis. Cold Spring Harb Perspect Med, 5(10), a022822. CR - Pourahmad, J., Hosseini, M.J., Bakan, S., et al. (2011). Hepatoprotective activity of angiotensin-converting enzyme (ACE) inhibitors, captopril and enalapril, against paraquat toxicity. Pestic Biochem Physiol, 99(1), 105-10. https://doi.org/10.1016/j.pestbp.2010.11.006 CR - Singh, N., Vijayanti, S., Saha, L. (2018). Targeting crosstalk between Nuclear factor (erythroid-derived 2)-like 2 and Nuclear factor kappa beta pathway by Nrf2 activator dimethyl fumarate in epileptogenesis. Int J Neurosci, 128(10), 987-994.https://doi.org/10.1080/00207454.2018.1441149 CR - Sonsalla, P.K., Coleman, C., Wong, L.Y., et al. (2013). The angiotensin converting enzyme inhibitor captopril protects nigrostriatal dopamine neurons in animal models of parkinsonism. Exp Neurol, 250, 376-383. https://doi.org/10.1016/j.expneurol.2013.10.014 CR - Takemiya, T., Suzuki, K., Sugiura, H., et al. (2003). Inducible brain COX-2 facilitates the recurrence of hippocampal seizures in mouse rapid kindling. Prostaglandins Other Lipid Mediat, 71(3-4), 205-216. https://doi.org/10.1016/S1098-8823(03)00040-6 CR - Taşkıran, A.Ş., & Taştemur, Y. (2020). The comparison of inflammatory markers in pentylenetetrazole-induced acute epileptic seizure model and chronic epilepsy model in rats. Cumhuriyet Science Journal, 41(3), 635- 641. https://doi.org/10.17776/csj.735457 CR - Taskiran, A.S., Ergul, M., Gunes, H., et al. (2021). The Effects of Proton Pump Inhibitors (Pantoprazole) on Pentylenetetrazole-Induced Epileptic Seizures in Rats and Neurotoxicity in the SH-SY5Y Human Neuroblastoma Cell Line. Cell Mol Neurobiol, 41(1), 173-183. https://doi.org/10.1007/s10571-020-00956-6 CR - Taştemur, Y., Gumus, E., Ergül, M., et al. (2020). Positive effects of angiotensin-converting enzyme (ACE) inhibitor, captopril, on pentylenetetrazole-induced epileptic seizures in mice. Tropıcal Journal of Pharmaceutıcal Research, 19(3), 637-643.doi: 10.4314/tjpr.v19i3.26 CR - Vahidirad, M., Arab-Nozari, M., Mohammadi, H., et al. (2018). Protective effect of captopril against diazinon induced nephrotoxicity and neurotoxicity via inhibition of ROS-NO pathway. Drug Chem Toxico, 41(3), 287-293. https://doi.org/10.1080/01480545.2017.1391830 CR - Vezzan,i A., French, J., Bartfai, T., et al. (2011). The role of inflammation in epilepsy. Nat Rev Neurol, 7(1), 31-40. https://doi.org/10.1038/nrneurol.2010.178 CR - Vezzani, A., Aronica, E., Mazarati, A., et al. (2013). Epilepsy and brain inflammation. Exp Neurol, 244,11- 21. https://doi.org/10.1016/j.expneurol.2011.09.033 CR - Vezzani, A., Conti, M., De Luigi, A., et al. (1999). Interleukin-1beta immunoreactivity and microglia are enhanced in the rat hippocampus by focal kainate application. Functional evidence for enhancement of electrographic seizures. J Neurosci, 19(12), 5054-5065. https://doi.org/10.1523/JNEUROSCI.19-12-05054.1999 UR - https://doi.org/10.51972/tfsd.1333472 L1 - https://dergipark.org.tr/tr/download/article-file/3290106 ER -