Azilsartan ameliorates aluminium chloride induced Alzheimer’s disease like pathology

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease manifested with accumulation of neurotoxic proteins like beta-amyloid (Aβ) and hyperphosphorylated tau. Administration of angiotensin receptor blockers (ARBs) such as Telmisartan has demonstrated to generate significant memory improvement in AD. Azilsartan is an ARB with better bioavailability than Telmisartan. Hence, the present work evaluates the efficacy of Azilsartan against aluminium chloride (AlCl3) induced AD. In the work, albino rats were divided into five groups (n=6). Group I served as control and received saline (10 ml/kg). Group-II was treated with AlCl3 (100 mg/kg) for 42 days; Group-III and IV received Azilsartan (5 mg/kg) and Telmisartan (10 mg/kg) with AlCl3 daily for 42 days. Y-maze, elevated plus maze and radial arm maze were used to evaluate memory functions. This was followed by biochemical and histological studies, along-with determination of Aβ content and anti-oxidant status. AlCl3 was found to significantly (p <0.05) reduce cognition and increased concentration of Aβ in a hippocampus with elevated lipid peroxidation levels. It also significantly (p<0.05) decreased superoxide dismutase and increased malondialdehyde content. However, brain histology showed presence of neurofibrillary tangles, neuronal dead cells, and pyknotic cells compared to normal group. Still, Azilsartan and Telmisartan significantly (p<0.05) reversed cognitive dysfunction, improved antioxidant status and decreased Aβ production. Thus we conclude that Azilsartan protects AlCl3 induced AD-like pathology but, to a degree less than Telmisartan.

Keywords

• alzheimer’s
• memory
• neuroprotective
• amyloid-beta
• alcl3
• angiotensin