Erdogan Mumin Alper, Erdogan Arife, Erbas Oytun
Department of Physiology, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Turkey.
Department of Emergency Medicine, Izmir Bakırcay University Cigli Education and Research Hospital, Izmir, Turkey.
Neurochem Res. 2023 Jan;48(1):188-195. doi: 10.1007/s11064-022-03736-4. Epub 2022 Aug 30.
Epilepsy is a prevalent and frequently devastating neurological disorder defined by recurring spontaneous seizures caused by aberrant electrical activity in the brain. Over ten million people worldwide suffer from drug-resistant epilepsy. This severe condition requires novel treatment approaches. Both oxidative and nitrosative stress are thought to have a role in the etiology of epilepsy. Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that is used to treat type-2 diabetes mellitus. According to recent studies, Liraglutide also shows neuroprotective properties, improving memory retention and total hippocampus pyramidal neuronal population in mice. The purpose of this investigation was to determine the anti-seizure and anti-oxidative effects of liraglutide in a pentylenetetrazole (PTZ)-induced rat model of epilepsy. 48 rats were randomly assigned to two groups: those who had electroencephalography (EEG) recordings and those who underwent behavioral assessment. Rats received either intraperitoneal (IP) liraglutide at two different dosages (3-6 mg/kg) or a placebo, followed by pentylenetetrazole (IP). To determine if liraglutide has anti-seizure characteristics, we examined seizure activity in rats using EEG, the Racine convulsion scale (RCS), the time of first myoclonic jerk (FMJ), and MDA, SOD, TNF-α, IL-1β and GAD-67 levels. The mean EEG spike wave percentage score was reduced from 75.8% (placebo) to 59.4% (lower-dose) and 41.5% (higher-dose). FMJ had increased from a mean of 70.6 s (placebo) to 181.2 s (lower-dose) and 205.2 s (higher-dose). RCS was reduced from a mean of 5.5 (placebo) to 2.7 (lower-dose) and 2.4 (higher-dose). Liraglutide (3 and 6 mg/kg i.p.) successfully decreased the spike percentages and RCS associated with PTZ induced epilepsy, as well as considerably decreased MDA, TNF-α, IL-1β and elevated SOD, GAD-67 levels in rat brain. Liraglutide significantly decreased seizure activity at both dosages when compared to control, most likely due to its anti-oxidant and anti-inflammatory properties. The potential clinical role of liraglutide as an anti-seizure medication should be further explored.
癫痫是一种常见且往往具有破坏性的神经系统疾病，其定义为由大脑异常电活动引起的反复自发性癫痫发作。全球超过一千万人患有耐药性癫痫。这种严重状况需要新的治疗方法。氧化应激和亚硝化应激都被认为在癫痫的病因中起作用。利拉鲁肽是一种用于治疗2型糖尿病的胰高血糖素样肽-1（GLP-1）类似物。根据最近的研究，利拉鲁肽还显示出神经保护特性，可改善小鼠的记忆保持和海马体锥体神经元总数。本研究的目的是确定利拉鲁肽在戊四氮（PTZ）诱导的大鼠癫痫模型中的抗癫痫和抗氧化作用。48只大鼠被随机分为两组：进行脑电图（EEG）记录的大鼠和接受行为评估的大鼠。大鼠接受两种不同剂量（3 - 6mg/kg）的腹腔注射（IP）利拉鲁肽或安慰剂，随后注射戊四氮（IP）。为了确定利拉鲁肽是否具有抗癫痫特性，我们使用脑电图、拉辛惊厥量表（RCS）、首次肌阵挛抽搐时间（FMJ）以及丙二醛（MDA）、超氧化物歧化酶（SOD）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和谷氨酸脱羧酶-67（GAD-67）水平来检测大鼠的癫痫活动。脑电图尖波百分比平均得分从75.8%（安慰剂）降至59.4%（低剂量）和41.5%（高剂量）。FMJ从平均70.6秒（安慰剂）增加到181.2秒（低剂量）和205.2秒（高剂量）。RCS从平均5.5（安慰剂）降至2.7（低剂量）和2.4（高剂量）。利拉鲁肽（3mg/kg和6mg/kg腹腔注射）成功降低了与PTZ诱导的癫痫相关的尖波百分比和RCS，并且显著降低了大鼠脑中的MDA、TNF-α、IL-1β水平，提高了SOD、GAD-67水平。与对照组相比，两种剂量的利拉鲁肽均显著降低了癫痫活动，这很可能归因于其抗氧化和抗炎特性。利拉鲁肽作为抗癫痫药物的潜在临床作用应进一步探索。
