Possible combined effect of perindopril and Azilsartan in an experimental model of dementia in rats

Abstract

Renin-angiotensin system exerted deleterious effects on learning and cognitive functions through different mechanisms. The present study has been designed to evaluate the protective effect of perindopril and azilsartan as monotherapy or in combination on aluminum chloride (AlCl ₃) induced neurobehavioral and pathological changes in Alzheimeric rats. Male Wistar rats were divided into nine groups (n = 6); negative control, AlCl3 treated, vehicle, AlCl3 and Azilsartan (3.5 mg/kg, 7 mg/kg) co-treated, AlCl3 and perindopril (0.5 mg/kg, 1 mg/kg) co-treated, AlCl3 and (Azilsartan 3.5 mg/kg + perindopril 0.5 mg/kg), and AlCl3 and (Azilsartan 7 mg/kg + perindopril 1 mg/kg), all groups were treated for consecutive 60 days. Then, memory function was evaluated by the Y- maze test. Amyloid Peptide − 42 (Aβ-42), Acetylcholinesterase (AChE), Malondialdehyde (MDA), Tumor necrosis factor (TNF-α) and Nitric Oxide (NO) levels in the hippocampus were assessed with (ELISA) kits. The histopathological studies of the hippocampal dentate gyrus (DG) and Cornu Ammonis-3 (CA3) were also performed. Oral administration of either azilsartan and perindopril alone or in combined for 60 days have shown; improvement of cognitive function, significant reduction in the hippocampal levels of Aβ-42, Acetylcholinesterase, Malondialdehyde (MDA), Tumor necrosis factor (TNF-α) and reserved most of histopathological changes in dentate gyrus (DG) and Cornu Ammonis-3 (CA3) that mediated by Alcl ₃. Our behavioral, biochemical, and histopathological studies indicate that perindopril and azilsartan have neuroprotective effects on the AD model of rats induced by AlCl ₃, suggesting that perindopril and azilsartan may be a candidate drugs for the treatment of AD.