Title:Levosimendan Prevents Memory Impairment Induced by Diabetes in Rats: Role of Oxidative Stress
VOLUME: 16 ISSUE: 14
Author(s):Abeer M. Rababa'h*, Karem H. Alzoubi, Sandy Baydoun and Omar F. Khabour
Affiliation:Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid 22110
Keywords:Streptozotocin, reactive oxygen species, levosimendan, diabetes mellitus, memory, hyperglycemia.
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.
