Anoush Mahdieh, Taghaddosi Neda, Bokaei Hosseini Zahra, Rahmati Fatemeh, Bijani Soroush, Kalantari-Hesari Ali, Hosseini Mir-Jamal
Zanjan Applied Pharmacology Research Center, Health and Metabolic Diseases Research Institute, Zanjan University of Medical Sciences, Zanjan, Iran.
Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
IBRO Neurosci Rep. 2025 Jan 10;18:163-170. doi: 10.1016/j.ibneur.2025.01.008. eCollection 2025 Jun.
Alzheimer's disease (AD) is one of the most common age-related neurodegenerative disorders. The main medicinal theory for the management of AD belongs to the acetyl-cholinesterase-inhibition pathway and NMDA antagonism. Recent investigation proposed memory improvement by sodium-glucose co-transporter 2 (SGLT2) inhibitors which indicated to improve glycemic control in adults with type 2 diabetes mellitus. According to the lack of sufficient evidence about the efficacy of empagliflozin (EMPA) for memory improvement, in comparison with donepezil (DON), the present research was carried out in order to investigate this hypothesis towards scopolamine-induced neurotoxicity on experimental male Wistar rats. The animals divided into two sets, each included 4 groups: The first set of Healthy animals [Control, EMPA (4 or 10 mg/kg), DON (1 mg/kg)]. The second set of rat Alzheimer model, which received 2 mg/kg Scopolamine by intraperitoneal route for 10 days followed by other treatments [AD, AD+ EMPA (4 or 10 mg/kg) and AD+DON]. Normal rats and AD rats, with each group receiving different substances for 8 consecutive days and 24 h after the accomplishment of the drug administrations, the memory functions assessed through Morris water maze (MWM) paradigm. This task was followed by decapitation of rats in order to evaluate the biochemical oxidative stress parameters in brain tissue. Our data indicated that EMPA significantly improved animals' performance in the behavioral test with a significant decrease in oxidative stress and antioxidant imbalance. In addition, EMPA (4 mg/kg) significantly reduced both cellular malondialdehyde and protein carbonyl content while conversely increased the total reduced glutathione content. Besides, the levels of total as well as endogenous antioxidants in the ferric reducing antioxidant power assay reported to be augmented. It seems that EMPA significantly improved both cellular biochemical aspects and memory performance in animal models in accordance with histopathological assessments. Conclusively, 4 mg/kg EMPA demonstrated better results in all aspects that were evaluated during this research.
阿尔茨海默病（AD）是最常见的与年龄相关的神经退行性疾病之一。治疗AD的主要医学理论属于乙酰胆碱酯酶抑制途径和N-甲基-D-天冬氨酸（NMDA）拮抗作用。最近的研究提出，钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂可改善记忆力，这表明其能改善2型糖尿病成年患者的血糖控制。鉴于关于恩格列净（EMPA）改善记忆力功效的证据不足，本研究将其与多奈哌齐（DON）进行比较，以探讨其对东莨菪碱诱导的实验性雄性Wistar大鼠神经毒性的影响。动物分为两组，每组包括4个组：第一组为健康动物[对照组、EMPA（4或10mg/kg）、DON（1mg/kg）]。第二组为大鼠阿尔茨海默病模型，通过腹腔注射2mg/kg东莨菪碱，持续10天，随后进行其他治疗[AD组、AD + EMPA（4或10mg/kg）组和AD + DON组]。正常大鼠和AD大鼠每组连续8天接受不同物质处理，给药完成后24小时，通过莫里斯水迷宫（MWM）范式评估记忆功能。该实验之后将大鼠断头，以评估脑组织中的生化氧化应激参数。我们的数据表明，EMPA显著改善了动物在行为测试中的表现，同时氧化应激和抗氧化失衡显著降低。此外，EMPA（4mg/kg）显著降低了细胞丙二醛和蛋白质羰基含量，同时相反地增加了总还原型谷胱甘肽含量。此外，在铁还原抗氧化能力测定中，总抗氧化剂以及内源性抗氧化剂的水平均有所增加。根据组织病理学评估，EMPA似乎显著改善了动物模型中的细胞生化方面和记忆表现。总之，4mg/kg EMPA在本研究评估的所有方面都显示出更好的结果。
