Unveiling the Protective Potential of Sugammadex against PTZ-Induced Epileptic Seizures in Mice: A Comprehensive Study on Oxidative Stress, Apoptosis, and Autophagy

IF 0.5 4区医学 Q4 NEUROSCIENCES

Neurochemical Journal Pub Date : 2024-05-27 DOI:10.1134/s1819712424020181

Mustafa Karademir, Aysegül Öztürk, Fatih Yulak, Mustafa Özkaraca, Ahmet Sevki Taskiran

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Abstract

Sugammadex (SUG) is a modified γ-cyclodextrin molecule used in patients under general anesthesia to reverse the effects of neuromuscular blocking agents. Besides, recent studies have shown that SUG positively affects the nervous system. However, its effect on seizures is still unclear. The current study aimed to examine the effects of SUG on pentylenetetrazole (PTZ)-induced epileptic seizures in mice. The mice were randomly divided into four groups. Group 1 was controlled, group 2 was administered saline (1 mL/kg serum physiologic), and Groups 3 and 4 were administered Sugammadex (150 and 300 mg/kg). Pentylenetetrazole (60 mg/kg) was given to induce seizures 30 min after saline or drug administration except for the control group. Total oxidant status (TOS) and total antioxidant status (TAS) levels in the hippocampus and cortex were measured using a commercial kit. 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxynonenal (4‑HNE), 3,3 dityrosine, caspase-3, apoptosis-inducing factor (AIF), and light chain 3 (LC3B) levels in the hippocampal CA1 region and cortex after seizures were evaluated immunohistochemical staining. SUG reduced seizure stages and increased epileptic seizure onset times. Moreover, it decreased TOS levels and increased TAS levels in the hippocampus and cortex. Besides, after seizures, it reduced 4-HNE, 3,3 dityrosandine, caspase-3, and LC3B immunohistochemical scores in the hippocampal CA1 region and cortex. SUG has protective effects on pentylenetetrazole-induced seizures in mice, alleviating seizures, oxidative stress, apoptosis, and autophagy. The anticonvulsant mechanism of SUG may be related to the inhibition of the oxidative stress pathway.

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揭示舒甘美对 PTZ 诱导的小鼠癫痫发作的保护潜力：关于氧化应激、细胞凋亡和自噬的综合研究

摘要舒降之（Sugammadex，SUG）是一种改性γ-环糊精分子，用于全身麻醉患者，以逆转神经肌肉阻滞剂的作用。此外，最近的研究表明，SUG 对神经系统有积极影响。然而，它对癫痫发作的影响仍不明确。本研究旨在探讨 SUG 对戊四唑（PTZ）诱导的小鼠癫痫发作的影响。小鼠被随机分为四组。第 1 组为对照组，第 2 组注射生理盐水（1 mL/kg 生理血清），第 3 和第 4 组注射舒格迈司（150 和 300 mg/kg）。除对照组外，在注射生理盐水或药物 30 分钟后注射戊四唑（60 毫克/千克）以诱发癫痫发作。海马和皮层中的总氧化状态（TOS）和总抗氧化状态（TAS）水平使用商业试剂盒进行测量。对癫痫发作后海马CA1区和皮层中的8-羟基脱氧鸟苷（8-OHdG）、4-羟基壬烯醛（4-HNE）、3,3-二酪氨酸、Caspase-3、凋亡诱导因子（AIF）和轻链3（LC3B）水平进行免疫组化染色评估。SUG 可减少癫痫发作阶段并延长癫痫发作开始时间。此外，它还降低了海马和皮层中的 TOS 水平，提高了 TAS 水平。此外，癫痫发作后，SUG 还能降低海马 CA1 区和皮层中的 4-HNE、3,3 dityrosandine、caspase-3 和 LC3B 免疫组化评分。SUG 对戊四唑诱导的小鼠癫痫发作具有保护作用，能缓解癫痫发作、氧化应激、细胞凋亡和自噬。SUG 的抗惊厥机制可能与抑制氧化应激途径有关。

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来源期刊

Neurochemical Journal 医学-神经科学

自引率

20.00%

发文量

审稿时长

>12 weeks

期刊介绍： Neurochemical Journal (Neirokhimiya) provides a source for the communication of the latest findings in all areas of contemporary neurochemistry and other fields of relevance (including molecular biology, biochemistry, physiology, neuroimmunology, pharmacology) in an afford to expand our understanding of the functions of the nervous system. The journal presents papers on functional neurochemistry, nervous system receptors, neurotransmitters, myelin, chromaffin granules and other components of the nervous system, as well as neurophysiological and clinical aspects, behavioral reactions, etc. Relevant topics include structure and function of the nervous system proteins, neuropeptides, nucleic acids, nucleotides, lipids, and other biologically active components. The journal is devoted to the rapid publication of regular papers containing the results of original research, reviews highlighting major developments in neurochemistry, short communications, new experimental studies that use neurochemical methodology, descriptions of new methods of value for neurochemistry, theoretical material suggesting novel principles and approaches to neurochemical problems, presentations of new hypotheses and significant findings, discussions, chronicles of congresses, meetings, and conferences with short presentations of the most sensational and timely reports, information on the activity of the Russian and International Neurochemical Societies, as well as advertisements of reagents and equipment.