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

Abstract

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.