Protective effects of levosimendan in scopolamineinduced mice model of Alzheimer's disease

Abstract

Objectives. Alzheimer's disease is the most prevalent neurodegenerative disease and accounts for approximately 70% of all dementia cases worldwide. Levosimendan is a positive inotropic agent with well-documented pleiotropic properties, including anti-inflammatory and antioxidant effects. The current research evaluated the possible effect of levosimendan alone or in combination with donepezil against scopolamine-induced mice models of Alzheimer’s disease. Material and methods. Mice were divided into five groups: the control group, the induction group (scopolamine 1 mg/kg/i.p once daily for 7 days), other groups that received the tested drugs prophylactically for 2 weeks and then induced with scopolamine together with the same doses of the tested drug for one week. These treatment groups included the levosimendan group (200 μg/kg i.p. once weekly for 3 weeks), the donepezil group (5 mg/kg i.p once daily for 3 weeks), and the fifth group received a combination of levosimendan (200 μg/ kg i.p. once weekly) and donepezil (5mg/kg i.p once daily). Cognitive performance was assessed by conducting behavioral tests (a novel objective recognition test and Y Maze test), and the levels of biological markers of oxidative stress (SOD and MDA), inflammatory cytokines (TNFα, IL1β and IL-6) and AChE in the brain tissue homogenate were measured utilizing available ELISA kits. Results. Levosimendan preserved the spatial memory and recognition function and significantly reduced: ACHE level, IL-6, IL-1β, TNF-α, and MDA levels, and significantly increased SOD level in mice brain tissue homogenate as compared to the induction group. And the combination of levosimendan with donepezil resulted in non-significant improvement as compared to each drug alone specifically in ACHE level reduction and oxidative stress markers. Conclusions. The current study showed that levosimendan produced a neuroprotective effect against the scopolamine-induced mice models of AD. This effect may be in part attributed to the antioxidant and anti-inflammatory properties of levosimendan.