TY  - JOUR
T1  - The effect of acute and chronic harmaline administration on penicillin-induced epileptiform activity in rats
TT  - Sıçanlarda akut ve kronik uygulanan harmalinin penisilin ile oluşturulmuş epileptiform aktivite üzerine etkisi
AU  - Özkan, Kayhan
AU  - Demir, Şerif
PY  - 2024
DA  - September
Y2  - 2024
DO  - 10.21673/anadoluklin.1433359
JF  - Anatolian Clinic the Journal of Medical Sciences
JO  - Anatolian Clin
PB  - Hayat Sağlık ve Sosyal Hizmetler Vakfı
WT  - DergiPark
SN  - 2149-5254
SP  - 304
EP  - 317
VL  - 29
IS  - 3
LA  - en
AB  - Aim: Harmaline (HR) is a monoamine oxidase inhibitor (MAOi) and antioxidant alkaloid obtained from Banisteriopsis caapi and Peganum harmala, where experimental studies have been conducted to support modern medicine. The electrophysiological impact of short-term and long-term HR treatment on the penicillin G-induced epileptic model in rats was examined in this study.Methods: Eighty-four adult male Wistar rats were randomly assigned to two groups: one received a single dose/day of HR, and the other received repeated doses/days of HR. Each group was further divided into six subgroups based on the dose of HR (10, 50, and 100 mg/kg). Epileptiform activity (EA) was triggered in the experimental groups with intracortical penicillin administration. Electrophysiological data were collected and analyzed using electrocorticography (ECoG). The serum levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) were measured using the Enzyme-Linked Immuno Sorbent Assay (ELISA) method to assess the free radical scavenger effects of HR. The latency, frequency, and amplitude of EA waves and serum antioxidant marker levels were analyzed statistically.Results: There was no observed EA in the sham group. Nevertheless, the results showed that both acute and chronic HR treatment increased the seizure threshold dose-dependently (p
KW  - Antioxidants
KW  - electrocorticography
KW  - epilepsy
KW  - harmaline
KW  - monoamine oxidase
N2  - Amaç: Harmalin (HR), modern tıbbı desteklemek amacıyla deneysel çalışmaların yapıldığı Banisteriopsis caapi ve Peganum harmala bitkilerinden elde edilen, monoamin oksidaz inhibitörü (MAOi) ve antioksidan bir alkaloiddir. Bu çalışmada kısa süreli ve uzun süreli HR tedavisinin sıçanlarda penisilin G ile indüklenen epileptik model üzerindeki elektrofizyolojik etkisi incelenmiştir.Yöntemler: Seksen dört yetişkin erkek Wistar sıçan rastgele iki gruba ayrıldı. Akut gruba tek doz/gün HR, kronik gruba tekrarlayan doz/gün HR verildi. Her grup ayrıca HR (10, 50 ve100 mg/kg) dozuna göre altı alt gruba ayrıldı. İntrakortikal penisilin uygulamasıyla deney gruplarında epileptiform aktivite (EA) tetiklendi. Elektrofizyolojik veriler, elektrokortikografi (ECoG) kullanılarak izlendi ve analiz edildi. HR’nin serbest radikal temizleyici etkilerini değerlendirmek için süperoksit dismutaz (SOD), katalaz (CAT), glutatyon peroksidaz (GPx) ve glutatyon redüktazın (GR) serum seviyeleri Enzim Bağlı İmmüno-Sorbent testi (ELISA) yöntemi kullanılarak ölçüldü. EA dalgalarının latensi, frekansı ve amplitüdü ile serum antioksidan belirteç düzeyleri istatistiksel olarak analiz edildi.Bulgular: Sham grubunda EA görülmedi. Ancak sonuçlar hem akut hem de kronik HR tedavisinin nöbet eşiğini doza bağlı olarak arttırdığını gösterdi (p
CR  - Lolk K, Lange T, Elwert F, Dreier JW, Christensen J. Traumatic brain injury, stroke, and epilepsy: A mediation study in a Danish nationwide cohort. Epilepsia. 2023;64(3):718-27.
CR  - Czuczwar SJ. Epilepsy [Internet]. Brisbane (AU): Exon Publications; 2022. pp. 50-71.
CR  - Löscher W, Potschka H, Sisodiya SM, Vezzani A. Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options. Pharmacol Rev. 2020;72(3):606-38.
CR  - Chen TS, Huang TH, Lai MC, Huang CW. The Role of Glutamate Receptors in Epilepsy. Biomedicines. 2023;11(3):783.
CR  - de Melo AD, Freire VAF, Diogo ÍL, Santos HL, Barbosa LA, de Carvalho LED. Antioxidant Therapy Reduces Oxidative Stress, Restores Na,K-ATPase Function and Induces Neuroprotection in Rodent Models of Seizure and Epilepsy: A Systematic Review and Meta-Analysis. Antioxidants (Basel). 2023;12(7):1397.
CR  - Marangoz C, Bağirici F. Effects of L-arginine on penicillin-induced epileptiform activity in rats. Jpn J Pharmacol. 2001;86(3):297-301.
CR  - Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475-82.
CR  - Im JH, Jin YR, Lee JJ, et al. Antiplatelet activity of beta-carboline alkaloids from Perganum harmala: a possible mechanism through inhibiting PLCgamma2 phosphorylation. Vascul Pharmacol. 2009;50(5-6):147-52.
CR  - Kaur J, Famta P, Famta M, et al. Potential anti-epileptic phytoconstituents: An updated review. J Ethnopharmacol. 2021;268:113565.
CR  - Song Y, Kesuma D, Wang J, et al. Specific inhibition of cyclin-dependent kinases and cell proliferation by harmine. Biochem Biophys Res Commun. 2004;317(1):128-32.
CR  - Rahimian Z, Sadrian S, Shahisavandi M, et al. Antiseizure Effects of Peganum harmala L. and Lavandula angustifolia. Biomed Res Int. 2023;2023:4121998.
CR  - 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.
CR  - Goldschen-Ohm MP. Benzodiazepine Modulation of GABAA Receptors: A Mechanistic Perspective. Biomolecules. 2022;12(12):1784.
CR  - Herraiz T, Guillén H. Monoamine Oxidase-A Inhibition and Associated Antioxidant Activity in Plant Extracts with Potential Antidepressant Actions. Biomed Res Int. 2018;2018:4810394.
CR  - Maan G, Sikdar B, Kumar A, Shukla R, Mishra A. Role of Flavonoids in Neurodegenerative Diseases: Limitations and Future Perspectives. Curr Top Med Chem. 2020;20(13):1169-94.
CR  - Łukawski K, Czuczwar SJ. Oxidative Stress and Neurodegeneration in Animal Models of Seizures and Epilepsy. Antioxidants (Basel). 2023;12(5):1049.
CR  - Shahrajabian MH, Sun W, Cheng Q. Improving health benefits with considering traditional and modern health benefits of Peganum harmala. Clin Phytosci. 2021;7(1):18-32.
CR  - Aricioglu F, Yillar O, Korcegez E, Berkman K. Effect of harmane on the convulsive threshold in epilepsy models in mice. Ann N Y Acad Sci. 2003;1009:190-5.
CR  - Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale, NJ: Erlbaum; 1988.
CR  - Larit F, León F. Therapeutics to Treat Psychiatric and Neurological Disorders: A Promising Perspective from Algerian Traditional Medicine. Plants (Basel). 2023;12(22):3860.
CR  - Nafisi S, Bonsaii M, Maali P, Khalilzadeh MA, Manouchehri F. Beta-carboline alkaloids bind DNA. J Photochem Photobiol B. 2010;100(2):84-91.
CR  - McDaniel SS, Wong M. Therapeutic role of mammalian target of rapamycin (mTOR) inhibition in preventing epileptogenesis. Neurosci Lett. 2011;497(3):231-9.
CR  - Vrabec R, Blunden G, Cahlíková L. Natural Alkaloids as Multi-Target Compounds towards Factors Implicated in Alzheimer’s Disease. Int J Mol Sci. 2023;24(5):4399.
CR  - Doskaliyev A, Seidakhmetova R, Tutai DS, Goldaeva K, Surov V, Adekenov S. Alkaloids of Peganum harmala L. and their Pharmacological Activity. Open Access Maced J Med Sci. 2021;9(A):766-75.
CR  - Jewett BE, Thapa B. Physiology, NMDA Receptor. Treasure Island (FL): StatPearls Publishing; 2022. pp. 20-56.
CR  - Golub VM, Reddy DS. Post-Traumatic Epilepsy and Comorbidities: Advanced Models, Molecular Mechanisms, Biomarkers, and Novel Therapeutic Interventions. Pharmacol Rev. 2022;74(2):387-438.
CR  - Rodríguez L, López A, Moyna G, et al. New Insights into the Chemical Composition of Ayahuasca. ACS Omega. 2022;7(14):12307-17.
CR  - Baru Venkata R, Prasanth DSNBK, Pasala PK, et al. Utilizing Andrographis paniculata leaves and roots by effective usage of the bioactive andrographolide and its nanodelivery: investigation of antikindling and antioxidant activities through in silico and in vivo studies. Front Nutr. 2023;10:1185236.
CR  - Trindade-Filho EM, de Castro-Neto EF, de A Carvalho R, et al. Serotonin depletion effects on the pilocarpine model of epilepsy. Epilepsy Res. 2008;82(2-3):194-9.
CR  - Abdulrahman M, Alshahrani M. Antiepileptic effect of ethanolic extract of seeds of Peganum harmala on maximal electroshock seizure model in albino mice. Int J Allied Med Sci Clin Res. 2016;4(3):529-35.
CR  - Tsabang N, Guedje NM, Fokunang C, et al. Ethnopharmacological and Ethnomedical Study of Anti-Epileptic Plants used in Traditional Medicine in Yaounde and its Surroundings Areas (Cameroon). J Biol Chem Res. 2016;33(1):496-509.
CR  - Marwat SK, Rehman F. Medicinal and Pharmacological Potential of Harmala (Peganum harmala L.) Seeds. Nuts and Seeds in Health and Disease Prevention. Academic Press: San Diego, USA; 2011. pp. 585-599.
CR  - Thurman DJ, Beghi E, Begley CE, et al. Standards for epidemiologic studies and surveillance of epilepsy. Epilepsia. 2011;52 Suppl 7:2-26.
CR  - Grosso C, Santos M, Barroso MF. From Plants to Psycho-Neurology: Unravelling the Therapeutic Benefits of Bioactive Compounds in Brain Disorders. Antioxidants (Basel). 2023;12(8):1603.
CR  - Dewanjee S, Sohel M, Hossain MS, et al. A comprehensive review on clinically proven natural products in the management of nerve pain, with mechanistic insights. Heliyon. 2023;9(5):e15346.
CR  - Ethemoglu MS, Kutlu S, Seker FB, Erdogan CS, Bingol CA, Yilmaz B. Effects of agomelatine on electrocorticogram activity on penicillin-induced seizure model of rats. Neurosci Lett. 2019;690:120-125.
CR  - Ghasemi M, Schachter SC. The NMDA receptor complex as a therapeutic target in epilepsy: a review. Epilepsy Behav. 2011;22(4):617-40.
CR  - Handforth A. Harmaline tremor: underlying mechanisms in a potential animal model of essential tremor. Tremor Other Hyperkinet Mov (N Y). 2012;2:02-92-769-1.
CR  - Marangoz C, Bağirici F. Effects of L-arginine on penicillin-induced epileptiform activity in rats. Jpn J Pharmacol. 2001;86(3):297-301.
CR  - de Melo AD, Freire VAF, Diogo ÍL, Santos HL, Barbosa LA, de Carvalho LED. Antioxidant Therapy Reduces Oxidative Stress, Restores Na,K-ATPase Function and Induces Neuroprotection in Rodent Models of Seizure and Epilepsy: A Systematic Review and Meta-Analysis. Antioxidants (Basel). 2023;12(7):1397.
CR  - Ngugi AK, Kariuki SM, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Incidence of epilepsy: a systematic review and meta-analysis. Neurology. 2011;77(10):1005-12.
CR  - Pimpinella G, Palmery M. Interaction of beta-carbolines with central dopaminergic transmission in mice: structure-activity relationships. Neurosci Lett. 1995;189(2):121-4.
CR  - Yildirim M, Marangoz AH, Ayyildiz M, Ankarali S, Marangoz C. The interactions of nitric oxide and adenosine on penicillin-induced epileptiform activity in rats. Acta Neurobiol Exp (Wars). 2011;71(2):208-19.
UR  - https://doi.org/10.21673/anadoluklin.1433359
L1  - https://dergipark.org.tr/tr/download/article-file/3713478
ER  -