The current investigation aimed at studying the anti-epileptogenic effect of sitagliptin. The possible effect of the drug in combination with pregabalin in pentylenetetrazole (PTZ)- induced seizures was studied. In addition, the postulated mechanisms that could mediate such effect were explored namely, suppression of oxidative stress and neuro-inflammatory markers, autophagy and apoptosis. Seven days prior to PTZ (60 mg/kg, sc) injection, mice were treated with sitagliptin (5, 15, and 60 mg/kg, twice daily, orally) or pregabalin (30 mg/kg, once daily, orally) or their combination. At the end of the experiment, several parameters were assessed including: oxidative/nitro-oxidative stress such as superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GP-x) catalase (CAT), and lipid peroxidation assessed as malondialdehyde (MDA), nitrate/nitrite (NOx), 3-nitrotyrosine (3-NT). Seizure latency was evaluated. Neuronal damage was also assessed by performing tissue staining by hematoxylin and eosin, estimating hippocampus level of glutamate, gamma-aminobutyric acid (GABA), glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF). Also, markers for inflammation, autophagy and apoptosis were measured, nuclear factor erythroid-derived 2- like 2 (Nrf2), nuclear factor kappa-B (NF-κB), phosphatidylethanolamine-conjugated form of microtubule-associated protein light chain-3 (LC3-II), casapase-3, Bcl-2-like protein 4 (BAX) and glucagon like peptide-1 (GLP-1) activity. Sitagliptin significantly suppressed epileptogenesis in PTZ-induced seizures. Sitagliptin counteracted neuronal damage and all biochemical, and histo-chemical alteration induced by PTZ. Also, a more significant protective effect was observed after combination with pregabalin. This study is indicative for the antiepileptogenic potential of sitagliptin with or without pregabalin in the PTZ model of epilepsy which is likely to be through its effect on antioxidant, anti-apoptotic and autophagic pathways.

当前的研究旨在研究西他列汀的抗癫痫发生作用。研究了该药物与普瑞巴林组合在戊烯四唑（PTZ）诱发的癫痫发作中的可能作用。此外，探索了可能介导这种作用的机制，即抑制氧化应激和神经炎性标志物，自噬和细胞凋亡。在PTZ（60 mg / kg，sc）注射前7天，用西他列汀（5、15和60 mg / kg，每天两次，口服）或普瑞巴林（30 mg / kg，每天一次，口服）或他们的组合。在实验结束时，评估了几个参数，包括：氧化/硝基氧化应激，例如超氧化物歧化酶（SOD），还原型谷胱甘肽（GSH），谷胱甘肽过氧化物酶（GP-x）过氧化氢酶（CAT），脂质过氧化评估为丙二醛（MDA），硝酸盐/亚硝酸盐（NOx），3-硝基酪氨酸（3-NT）。评估癫痫潜伏期。还通过苏木精和曙红进行组织染色，估计海马谷氨酸，γ-氨基丁酸（GABA），神经胶质纤维酸性蛋白（GFAP）和脑源性神经营养因子（BDNF）来评估神经元损伤。此外，还测量了炎症，自噬和细胞凋亡的标志物，核因子类红血球来源的2-like 2（Nrf2），核因子κ-B（NF-κB），磷脂酰乙醇胺结合的微管相关蛋白轻链-3（ LC3-II），casapase-3，Bcl-2-样蛋白4（BAX）和胰高血糖素样肽-1（GLP-1）活性。西他列汀可显着抑制PTZ诱发的癫痫发作中的癫痫发生。西他列汀可抵消PTZ诱导的神经元损害和所有生化及组织化学改变。另外，与普瑞巴林组合后观察到更明显的保护作用。这项研究表明西他列汀在有或没有普瑞巴林的癫痫患者的PTZ模型中具有抗癫痫作用的潜力，这很可能是由于其对抗氧化剂，抗凋亡和自噬途径的影响。