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, reactive oxygen species, levosimendan, diabetes mellitus, memory, hyperglycemia.
[http://dx.doi.org/10.2147/DDDT.S3321] [PMID: 19920937]
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.08.015] [PMID: 16223548]
[http://dx.doi.org/10.1016/S0014-2999(02)01486-3] [PMID: 12007915]
[http://dx.doi.org/10.5001/omj.2012.68] [PMID: 23071876]
[http://dx.doi.org/10.2337/dc11-0442] [PMID: 21617109]
[http://dx.doi.org/10.2337/diacare.27.5.1047] [PMID: 15111519]
[http://dx.doi.org/10.2337/diabetes.52.10.2570] [PMID: 14514642]
[http://dx.doi.org/10.1016/S0074-7742(02)50080-5] [PMID: 12198813]
[http://dx.doi.org/10.1155/2012/302682] [PMID: 22645603]
[http://dx.doi.org/10.1007/s12031-013-0061-1] [PMID: 23832486]
[http://dx.doi.org/10.3390/ijms14023265] [PMID: 23385234]
[http://dx.doi.org/10.1139/cjpp-2012-0251] [PMID: 23537434]
[http://dx.doi.org/10.1111/j.1399-5448.2008.00431.x] [PMID: 19067891]
[http://dx.doi.org/10.1016/S0891-5849(00)00338-5] [PMID: 10980405]
[http://dx.doi.org/10.2337/diabetes.53.2007.S96] [PMID: 14749273]
[http://dx.doi.org/10.1016/j.bbr.2009.05.025] [PMID: 19482049]
[http://dx.doi.org/10.1111/jnc.12247] [PMID: 23521165]
[http://dx.doi.org/10.1016/j.bbr.2011.09.017] [PMID: 21944940]
[http://dx.doi.org/10.1097/FBP.0000000000000362] [PMID: 29176443]
[http://dx.doi.org/10.1177/1545968309348318] [PMID: 19841436]
[http://dx.doi.org/10.1002/jnr.490260116] [PMID: 2162971]
[http://dx.doi.org/10.2174/1570159X11666131120223201] [PMID: 24669211]
[http://dx.doi.org/10.1002/hipo.22135] [PMID: 23592546]
[http://dx.doi.org/10.1016/j.physbeh.2017.12.002] [PMID: 29217357]
[http://dx.doi.org/10.2165/00003495-200161050-00006] [PMID: 11368286]
[http://dx.doi.org/10.4103/0971-9784.173020] [PMID: 26750674]
[http://dx.doi.org/10.1111/jocs.12562] [PMID: 25989324]
[http://dx.doi.org/10.3402/ljm.v10.29269] [PMID: 26649830]
[http://dx.doi.org/10.1186/1475-2840-11-4] [PMID: 22239823]
[http://dx.doi.org/10.1111/jcpt.12067] [PMID: 23594161]
[http://dx.doi.org/10.2147/vhrm.2006.2.4.389] [PMID: 17323593]
[http://dx.doi.org/10.1053/j.jvca.2015.03.023] [PMID: 26275522]
[http://dx.doi.org/10.1186/1471-2377-10-97] [PMID: 20964834]
[http://dx.doi.org/10.1007/s00134-006-0519-5] [PMID: 17262190]
[http://dx.doi.org/10.1016/S0928-0987(99)00048-2] [PMID: 10494001]
[http://dx.doi.org/10.1186/1471-2377-12-81] [PMID: 22920500]
[http://dx.doi.org/10.2165/00003088-200746070-00001] [PMID: 17596101]
[http://dx.doi.org/10.2174/138920009787522142] [PMID: 19275545]
[http://dx.doi.org/10.1002/0471141755.ph0547s70]
[http://dx.doi.org/10.1007/s40200-019-00445-8] [PMID: 31890680]
[http://dx.doi.org/10.1007/BF01745791] [PMID: 5383655]
[http://dx.doi.org/10.1016/j.brainresbull.2015.02.002] [PMID: 25724146]
[http://dx.doi.org/10.1016/j.bbr.2012.09.018] [PMID: 23000531]
[http://dx.doi.org/10.1002/(SICI)1098-1063(1999)9:5<542:AID-HIPO8>3.0.CO;2-N] [PMID: 10560925]
[http://dx.doi.org/10.1016/j.brainresbull.2017.04.004] [PMID: 28433816]
[http://dx.doi.org/10.2337/diab.45.9.1259] [PMID: 8772732]
[http://dx.doi.org/10.1007/s001250051335] [PMID: 10819245]
[http://dx.doi.org/10.2337/diacare.18.5.681] [PMID: 8586007]
[http://dx.doi.org/10.1093/brain/awn288] [PMID: 19015157]
[http://dx.doi.org/10.1016/j.neuint.2012.07.025] [PMID: 22898296]
[http://dx.doi.org/10.1007/s12031-012-9881-7] [PMID: 22956188]
[http://dx.doi.org/10.1016/j.jams.2012.09.003] [PMID: 23265080]
[http://dx.doi.org/10.1093/gerona/63.5.505] [PMID: 18511755]
[http://dx.doi.org/10.1002/jbt.10058] [PMID: 12616644]
[http://dx.doi.org/10.1677/joe.1.06269] [PMID: 16214939]
[http://dx.doi.org/10.1016/j.ejphar.2006.03.024] [PMID: 16626697]
[http://dx.doi.org/10.1016/j.lfs.2008.05.013] [PMID: 18585396]
[PMID: 22754685]
[http://dx.doi.org/10.1007/978-3-642-45106-5_9] [PMID: 24668475]
[http://dx.doi.org/10.1016/j.pbb.2003.10.020] [PMID: 14751447]
[http://dx.doi.org/10.1021/bi00463a024] [PMID: 2161256]
[http://dx.doi.org/10.1179/1743132814Y.0000000428] [PMID: 25082546]
[http://dx.doi.org/10.1111/bcpt.12004] [PMID: 22938184]
[http://dx.doi.org/10.1016/j.ijporl.2019.04.004] [PMID: 30978472]
[http://dx.doi.org/10.1002/lt.23799] [PMID: 24273004]
[http://dx.doi.org/10.1007/s00232-012-9489-4] [PMID: 22843162]