The Effects of Proton Pump Inhibitors (Pantoprazole) on Pentylenetetrazole-Induced Epileptic Seizures in Rats and Neurot
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ORIGINAL RESEARCH
The Effects of Proton Pump Inhibitors (Pantoprazole) on Pentylenetetrazole‑Induced Epileptic Seizures in Rats and Neurotoxicity in the SH‑SY5Y Human Neuroblastoma Cell Line Ahmet Sevki Taskiran1 · Mustafa Ergul2 · Handan Gunes1 · Aysegul Ozturk1 · Bilal Sahin1 · Ercan Ozdemir1 Received: 10 July 2020 / Accepted: 22 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords Epilepsy · Pentylenetetrazole · Pantoprazole · Rats · SH-SY5Y
Introduction Seizure is a temporary dysfunction of the brain caused by an excessive and abnormal discharge of cortical neurons. Epilepsy is a central nervous system disorder characterized by repetitive seizures that usually occur without provocation due to a genetic predisposition or an underlying chronic pathological condition (Tastemur et al. 2020). It is one of the most common neurological disorders and affects about 1% of the world’s population (Taskıran et al. 2018). Epileptic seizures are related to a change in ion transport mechanisms in neuronal networks and directly cause the imbalance of the excitation–inhibition and indirectly cause oxidative stress * Ahmet Sevki Taskiran [email protected] 1
Department of Physiology, Sivas Cumhuriyet University School of Medicine, 58140 Sivas, Turkey
Department of Biochemistry, Sivas Cumhuriyet University School of Pharmacy, Sivas, Turkey
2
and neuroinflammation (Staley 2015). The frequent incidence of epileptic seizures significantly declines the learning and memory capacity in patients with epilepsy. It has been
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