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The Effects of Proton Pump Inhibitors (Pantoprazole) on Pentylenetetrazole-Induced Epileptic Seizures in Rats and Neurotoxicity in the SH-SY5Y Human Neuroblastoma Cell Line.
Cellular and Molecular Neurobiology ( IF 3.6 ) Pub Date : 2020-08-29 , DOI: 10.1007/s10571-020-00956-6
Ahmet Sevki Taskiran 1 , Mustafa Ergul 2 , Handan Gunes 1 , Aysegul Ozturk 1 , Bilal Sahin 1 , Ercan Ozdemir 1
Affiliation  

Recent studies have shown that proton pump inhibitors have positive effects on the nervous system. However, its effect on epileptic seizure and neuronal damage are still unclear. In this study, it was aimed to investigate the effect of pantoprazole on pentylenetetrazole-induced epileptic seizures in rats and neurotoxicity in the SH-SY5Y cell line. Animals were divided into three groups: control, saline (1 mL/kg serum physiologic), and pantoprazole (10 mg/kg). Pentylenetetrazole (45 mg/kg) was given to induce a seizure and a passive avoidance test trial was carried out to evaluate memory function. 8-hydroxy-2′-deoxyguanosine (8-OHdG), caspase-3, and brain-derived neurotrophic factor (BDNF) levels were measured in the brain by commercial kits. SH-SY5Y cells were treated with saline or pantoprazole for one hour, and then pentylenetetrazole (30 µm) was added to the medium to induce neurotoxicity. After 24 h, cell viability, total antioxidant, total oxidant status, and apoptosis were measured in SH-SY5Y cells. It was found that pantoprazole treatment postponed epileptic seizure onset, protected memory, reduced 8-OHdG, caspase-3, and also increased BDNF in the brain. In addition, it blocked pentylenetetrazole toxicity, apoptosis, increased antioxidant, and decreased oxidant status in SH-SY5Y cells. Pantoprazole significantly improved seizure, oxidative stress, and apoptosis. Thus, pantoprazole could be used as a supportive therapeutic agent in epilepsy.



中文翻译:


质子泵抑制剂(泮托拉唑)对戊四唑诱导的大鼠癫痫发作的影响以及 SH-SY5Y 人神经母细胞瘤细胞系的神经毒性。



最近的研究表明,质子泵抑制剂对神经系统具有积极作用。然而,其对癫痫发作和神经元损伤的影响仍不清楚。本研究旨在探讨泮托拉唑对戊四唑诱导的大鼠癫痫发作的影响以及对 SH-SY5Y 细胞系的神经毒性。将动物分为三组:对照组、盐水组(1 mL/kg 血清生理学)和泮托拉唑(10 mg/kg)。给予戊四唑(45 mg/kg)以诱发癫痫发作,并进行被动回避试验以评估记忆功能。通过商业试剂盒测量大脑中的 8-羟基-2'-脱氧鸟苷 (8-OHdG)、caspase-3 和脑源性神经营养因子 (BDNF) 水平。 SH-SY5Y细胞用盐水或泮托拉唑处理一小时,然后将戊四唑(30μm)添加到培养基中以诱导神经毒性。 24小时后,测量SH-SY5Y细胞的细胞活力、总抗氧化剂、总氧化剂状态和细胞凋亡。研究发现,泮托拉唑治疗可推迟癫痫发作,保护记忆,减少 8-OHdG、caspase-3,并增加大脑中的 BDNF。此外,它还可以阻断 SH-SY5Y 细胞中戊四唑的毒性、细胞凋亡、增加抗氧化剂并降低氧化状态。泮托拉唑显着改善癫痫发作、氧化应激和细胞凋亡。因此,泮托拉唑可用作癫痫的支持治疗剂。

更新日期:2020-08-29
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