Sıçanlarda akut ve kronik uygulanan harmalinin penisilin ile oluşturulmuş epileptiform aktivite üzerine etkisi

Year 2024, Volume: 29 Issue: 3, 304 - 317, 23.09.2024

Kayhan Özkan , Şerif Demir

https://doi.org/10.21673/anadoluklin.1433359

Abstract

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<0.05). Akut HR grubu kontrol ve diğer gruplarla karşılaştırıldığında diken dalga deşarjlarının sıklığı ve genliğinde 10. periyoda kadar düşürürken, kalan periyotlarda bu parametreleri etkilemediği gözlendi. Kronik gruplarda diken dalga frekansı ve diken dalga genliği açısından bazı zaman dilimleri dışında anlamlı fark görülmedi. Ayrıca kronik HR grubunun antioksidan enzim düzeylerinde kontrol ve diğer gruplara göre anlamlı bir artış görülürken (P<0.05) akut gruplarda anlamlı fark oluşmadı.

Sonuç: Harmalinin Kronik HR gruplarında ve akut HR gruplarının 10. periyotundan sonra diken dalga frekanslarını ve genliklerini etkilemediği görüldü. HR akut ve kronik gruplarda ilk EA başlama latensini uzattı ve uzun süreli kullanımda antioksidan etkiye sahip olabilir.

Keywords

Antioksidanlar, elektrokortikografi, epilepsi, harmalin, monoamin oksidaz

Project Number

BAP-2018.04.01.851.

The effect of acute and chronic harmaline administration on penicillin-induced epileptiform activity in rats

Abstract

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<0.05). It was observed that the acute HR group reduced the frequency and amplitude of spike-wave discharges up to the 10th period, compared to the control and other groups, and did not affect these parameters in the remaining periods. No significant difference was observed in the chronic groups in terms of spike wave frequency and spike-wave amplitude, except for some time periods. In addition, while there was a significant increase in antioxidant enzyme levels of the chronic HR group compared to the control and other groups (P<0.05), there was no significant difference in the acute groups.

Conclusion: It was observed that HR did not affect spike wave frequencies and amplitudes in all acute groups, except for the 10th period and in chronic HR groups. HR prolonged the latency to first EA onset in acute and chronic groups and may have an antioxidant effect with long-term use.

Keywords

Antioxidants, electrocorticography, epilepsy, harmaline, monoamine oxidase

Ethical Statement

The study received ethical approval from the Düzce University Animal Research Local Ethics Committee under the code 20180.1.1.

Supporting Institution

Bu tez Düzce Üniversitesi Bilimsel Araştırma Projeleri Yönetim Birimi Komisyonu Başkanlığı tarafından BAP-2018.04.01.851 numaralı proje ile desteklenmiştir.

Project Number

BAP-2018.04.01.851.

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