Levosimendan Prevents Memory Impairment Induced by Diabetes in Rats: Role of Oxidative Stress

Abstract

Background: Levosimendan is a calcium sensitizer and phosphodiesterase inhibitor that has potent antioxidant and anti-inflammatory activities.

Objectives: The aim of the current study is to investigate the potential protective effect of levosimendan on learning and memory impairment induced by diabetes.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Streptozotocin; diabetes mellitus; hyperglycemia; levosimendan; memory; reactive oxygen species..