Neuroprotective effects of empagliflozin against scopolamine-induced memory impairment and oxidative stress in rats

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.