Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.
Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan.
Curr Alzheimer Res. 2019;16(14):1300-1308. doi: 10.2174/1567205017666200102153239.
Levosimendan is a calcium sensitizer and phosphodiesterase inhibitor that has potent antioxidant and anti-inflammatory activities.
The aim of the current study is to investigate the potential protective effect of levosimendan on learning and memory impairment induced by diabetes.
Adult Wister rats were randomly divided into four groups (n=15 rats/group): control, levosimendan, streptozotocin (STZ) induced diabetes, and levosimendan-STZ diabetes. Upon confirmation of the success of the STZ diabetic model, intraperitoneal levosimendan (100µg/kg/week) was administrated to the assigned groups for 4 weeks. Then, the radial arm water maze was used to evaluate spatial learning and memory. Oxidative stress biomarkers and brain-derived neurotrophic factor were evaluated in hippocampal tissues.
The results showed that Diabetes Mellitus (DM) impaired both short- and long- term memory (P<0.01), while levosimendan protected the animals from memory impairment. In addition, levosimendan prevented DM-induced reduction in the hippocampal levels of superoxide dismutase and glutathione peroxidase (P<0.05). Moreover, the administration of levosimendan prevented DM-induced increases in hippocampal thiobarbituric acid reactive substances level (P<0.05). Furthermore, levosimendan restored the ratio of reduced/oxidized glutathione (GSH/GSSG) in DM rats to that observed in the control group (P<0.05).
In summary, DM induced learning and memory impairment, and treatment with levosimendan impeded this impairment probably through preventing alterations in the antioxidant system in the hippocampus.
左西孟旦是一种钙增敏剂和磷酸二酯酶抑制剂，具有很强的抗氧化和抗炎活性。
本研究旨在探讨左西孟旦对糖尿病引起的学习记忆障碍的潜在保护作用。
成年 Wistar 大鼠随机分为四组（每组 15 只大鼠）：对照组、左西孟旦组、链脲佐菌素（STZ）诱导的糖尿病组和左西孟旦-STZ 糖尿病组。STZ 糖尿病模型成功后，腹腔内给予左西孟旦（100µg/kg/周），共 4 周。然后，使用放射臂水迷宫评估空间学习和记忆。评估海马组织中的氧化应激生物标志物和脑源性神经营养因子。
结果表明，糖尿病（DM）损害了短期和长期记忆（P<0.01），而左西孟旦可保护动物免受记忆障碍的影响。此外，左西孟旦可预防 DM 引起的海马超氧化物歧化酶和谷胱甘肽过氧化物酶水平降低（P<0.05）。此外，左西孟旦可预防 DM 引起的海马硫代巴比妥酸反应物质水平升高（P<0.05）。此外，左西孟旦可将 DM 大鼠的还原/氧化型谷胱甘肽（GSH/GSSG）比值恢复至对照组水平（P<0.05）。
总之，DM 可引起学习和记忆障碍，而左西孟旦的治疗可能通过防止海马抗氧化系统的改变来阻止这种障碍。
