Ersin BEYAZÇİÇEK, Duru Aslıhan AVCİ, Özge BEYAZÇİÇEK

Sıçanlarda kronik uygulanan timokinonun penisilin ile oluşturulmuş epileptiform aktivite üzerine etkileri

Amaç: Timokinon (TQ), geleneksel bir tıbbi bitki olan ve geleneksel tıpta baharat ve ilaç olarak kullanılan Nigella sativa (NS)’den elde edilmiştir. Bu çalışmanın amacı, antikanser, antioksidan ve nöroprotektif etkileri bilinen TQ’nun sıçanlarda deneysel penisilin kaynaklı epilepsi modelinde kronik etkilerini araştırmaktır.Yöntemler: Bu çalışmada kırk dokuz adet erişkin erkek Wistar sıçan kullanıldı. Sıçanlar sham (S), kontrol (penisilin, CONT), diazepam (DZM), 10 mg/kg TQ (TQ10), 50 mg/kg TQ (TQ50), 10 mg/kg TQ+DZM (TQ10+DZM) ve 50 mg/kg TQ+DZM (TQ50+DZM) olmak üzere 7 gruba ayrıldı. TQ, 21 gün süresince intraperitoneal olarak uygulandı. Penisilin intrakortikal uygulanması ile epileptiform aktivite (EA) oluşturuldu. Kayıtlardan elde edilen elektrokortikografik veriler analiz edildi. EA dalgalarının latansı, frekansı ve amplitüdü istatistiksel olarak analiz edildi.Bulgular: Sham grubunda EA gözlemlenmedi. Ancak TQ10 ve TQ50 gruplarının ilk diken-dalga latansının CONT grubuna göre anlamlı olarak arttığı gözlendi. Diken-dalga frekansı ve diken-dalga amplitüdü bakımından bazı zaman periyotları dışında gruplar arasında istatistiksel olarak anlamlı fark yoktu.Sonuç: Sıçanlarda deneysel penisilinle oluşturulmuş EA modelinde kronik TQ uygulamasının, epileptik nöbetleri temsil eden herhangi bir diken dalga frekansını ve amplitüdünü etkilemediği gözlendi. Ancak, TQ›nun ilk EA başlama süresini uzattığı belirlendi.

Anahtar Kelimeler:

elektrokortikografi;, epilepsi;, nigella sativa, sıçan, timokinon

Effects of chronic administration of thymoquinone on penicillin induced epileptiform activity in rats

Aim: Thymoquinone (TQ) is derived from Nigella Sativa (NS) which is a traditional medicinal plant used as a spice, and medication in traditional medicine. This study aims to investigate the chronic effects of TQ, which has been shown anticancer, antioxidant, and neuroprotective effects, on experimental penicillin-induced epilepsy models in rats.Methods: Forty-nine adult male Wistar rats were used in this study. The rats were divided into 7 groups as; sham (S), control (penicillin, CONT), diazepam (DZM), 10 mg/kg TQ (TQ10), 50 mg/kg TQ (TQ50), 10 mg/kg TQ+DZM (TQ10+DZM) and 50 mg/kg TQ+DZM (TQ50+DZM). TQ was administered intraperitoneally for 21 days. Epileptiform activity (EA) was initiated by intracortical administration of penicillin. Electrocorticographic (ECoG) data obtained from the recordings were analyzed. The latency, frequency, and amplitude of EA waves were analyzed statistically.Results: There was no EA in the sham group. However, it was observed that the first spike-wave latency increased significantly in TQ10 and TQ50 groups compared to the CONT group. Except for some time periods, there was no significant difference between the groups according to spike-wave frequency, and spike-wave amplitude. Conclusion: It was observed that the application of chronic thymoquinone on the experimental penicillin-induced EA model in rats did not affect the frequency and amplitude of spike-wave representing epileptic seizures. However, TQ was found to prolong the latency of the first EA.

Keywords:

Electrocorticography epilepsy;, nigella sativa, rat;, thymoquinone, timokinon,

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Ankarali S, Beyazcicek E, Kilinc E, et al. The effect of rose oil on penicillin-induced epileptiform activity in rats: an electrophysiological study. Konuralp Tıp Derg. 2018;10(3):360–8.
You Y, Chen W, Li M, Zhang T, Jiang Y, Zheng X. Automatic focal and non-focal EEG detection using entropy-based features from flexible analytic wavelet transform. Biomed Signal Process Control. 2020;57:101761.
Feigin VL, Nichols E, Alam T, et al. Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(5):459–80.
Al-Naggar TB, Gómez-Serranillos MP, Carretero ME, Villar AM. Neuropharmacological activity of Nigella sativa L. extracts. J Ethnopharmacol. 2003;88(1):63–8.
Abdel-Fattah AFM, Matsumoto K, Watanabe H. Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. Eur J Pharmacol. 2000;400(1):89–97.
Verma R, Sartaj A, Qizilbash FF, et al. An Overview of the Neuropharmacological Potential of Thymoquinone and its Targeted Delivery Prospects for CNS Disorder. Curr Drug Metab. 2022;23(6):447–59.
Kaymak E, Akin AT, Öztürk E, Karabulut D, Kuloğlu N, Yakan B. Thymoquinone has a neuroprotective effect against inflammation, oxidative stress, and endoplasmic reticulum stress in the brain cortex, medulla, and hippocampus due to doxorubicin. J Biochem Mol Toxicol. 2021;35(11):e22888.
Pottoo FH, Ibrahim AM, Alammar A, et al. Thymoquinone: Review of Its Potential in the Treatment of Neurological Diseases. Pharm 2022, Vol 15, Page 408. 2022;15(4):408.
Meral I, Esrefoglu M, Dar KA, et al. Effects of Nigella sativa on apoptosis and GABAA receptor density in cerebral cortical and hippocampal neurons in pentylenetetrazol induced kindling in rats. Biotech Histochem 2016;91(8):493–500.
Fard AA, Saboory E, Tahmazi Y, Rasmi Y, Dindarian S, Parsamanesh N. Effect of orally-administrated thymoquinone during pregnancy on litter size, pentylenetetrazol-induced seizure, and body weight in rat offspring. Iran J Basic Med Sci. 2021;24(1):30.
Yildirim M, Marangoz AH, Ayyildiz M, Ankarali S, Marangoz C. The interactions of nitric oxide and adenosine on penicillininduced epileptiform activity in rats. Acta Neurobiol Exp (Wars). 2011;71(2):208–19.
Ögün MN, Çetinkaya A, Beyazçiçek E. The effect of vortioxetine on penicillin-induced epileptiform activity in rats. Arq Neuropsiquiatr. 2019;77(6):412–7.
Ankaralı S, Beyazçiçek E, Ankaralı H, Demir Ş. The Effect of Rapamycin on Penicillin- Induced Epileptiform Activity in Rats: An Electrophysiological Study/Rapamisinin Sıçanlarda Penisilinle Oluşturulmuş Epileptiform Aktivite Üzerine Etkisi: Bir Elektrofizyolojik Çalışma. Anadolu Klin Tıp Bilim Derg. 2016;21(3):197–206.
Beyazcicek E, Ankarali S, Beyazcicek O, Ankarali H, Demir S, Ozmerdivenli R. Effects of thymoquinone, the major constituent of Nigella sativa seeds, on penicillin-induced epileptiform activity in rats. Neurosciences. 2016;21(2):131–7.
Cakil D, Yildirim M, Ayyildiz M, Agar E. The effect of co-administration of the NMDA blocker with agonist and antagonist of CB1-receptor on penicillin-induced epileptiform activity in rats. Epilepsy Res. 2011;93(2–3):128–37.
Hosseinzadeh H, Parvardeh S, Nassiri-Asl M, Mansouri MT. Intracerebroventricular administration of thymoquinone, the major constituent of Nigella sativa seeds, suppresses epileptic seizures in rats. Med Sci Monit. 2005;11(4).
Raza M, Alghasham AA, Alorainy MS, El-Hadiyah TM. Potentiation of Valproate-induced Anticonvulsant Response by Nigella sativa Seed Constituents: The Role of GABA Receptors. Int J Health Sci (Qassim). 2008;2(1):15–25.
Beyazcicek E, Ankarali S, Beyazcicek O. the Effect of Thymoquinone on Penicillin-Induced Epileptiform Activity in Rats. Epilepsia. 2014;55(SI):193.
Benhelima A, Kaid-Omar Z, Hemida H, Benmahdi T, Addou A. Nephroprotective and diuretic effect of Nigella sativa L seeds oil on lithiasic wistar rats. African J Tradit Complement Altern Med. 2016;13(6):204–14.
Raza M, Alghasham AA, Alorainy MS, El-Hadiyah TM. Beneficial Interaction of Thymoquinone and Sodium Valproate in Experimental Models of Epilepsy: Reduction in Hepatotoxicity of Valproate. Sci Pharm. 2006;74(4):159–73.
Mostafa R, Moustafa Y, Science ZM. Thymoquinone alone or in combination with phenobarbital reduces the seizure score and the oxidative burden in pentylenetetrazole-kindled rats. 2012;185–92.
Ullah I, Badshah H, Naseer MI, Lee HY, Kim MO. Thymoquinone and vitamin C attenuates pentylenetetrazole-induced seizures via activation of GABAB1 receptor in adult rats cortex and hippocampus. Neuromolecular Med. 2015;17(1):35–46.
Brito S, Journal MR. Thymoquinone enhances neurogenesis to a greater extent in middle-aged than in young aged rat in chronic epilepsy. Faseb J. 2016;561–651.
Shao YY, Li B, Huang YM, Luo Q, Xie YM, Chen YH. Thymoquinone attenuates brain injury via an antioxidative pathway in a status epilepticus rat model. Transl Neurosci. 2017;8(1):9–14.
Lee WL, Hablitz JJ. Initiation of epileptiform activity by excitatory amino acid receptors in the disinhibited rat neocortex. J Neurophysiol. 1991;65(1):87–95.
Parsons CG, Stöffler A, Danysz W. Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system - too little activation is bad, too much is even worse. Neuropharmacology. 2007;53(6):699–723.
Krishek BJ, Moss SJ, Smart TG. A functional comparison of the antagonist bicuculline and picrotoxin at recombinant GABA(A) receptors. Neuropharmacology. 1996;35(9–10):1289–98.
Martin JH. The collective electrical behavior of cortical neurons: The electroencephalogram and the mechanisms of epilepsy. Princ Neural Sci. 1991;3:778–91.
Marangoz C, Ayyildiz M, Agar E. Evidence that sodium nitroprusside possesses anticonvulsant effects mediated through nitric oxide. Neuroreport. 1994;5(18):2454–6.
Chen RC, Huang YH, How SW. Systemic penicillin as an experimental model of epilepsy. Exp Neurol. 1986;92(3):533–40.