Potential Protective Effects of Angiotensin Ii Type 1 Receptor Blockade in Alzheimer Rat Model

Abstract

Background: Alzheimer disease (AD) and Alzheimer type dementia (ATD) represent major health problem in aged population. AD is characterized by memory impairment, exaggerated oxidative stress and decrease antioxidant capacity. Angiotensin II and angiotensin II type 1 and type 2 receptors (ATR 1 and ATR 2 ) are incriminated in the pathogenesis of AD.Aim of the work: This study was carried out to investigate the effect of angiotensin II type 1 receptor blockade on memory function in AlCl3-induced Alzheimer in rats.Materials and methods: Thirty animals in this study were divided into five equal groups. Group1: control rats. Group II: Alzheimer model, the rats were intraperitoneally injected with 40 mg / kilogram body AlCl3 for 4 weeks group III: ATR 1 blocker-treated AD-group: animals were injected telmisartan in a dose of 1mg/kg. by oral gavage for 8 weeks and for the last 4 weeks were injected AlCl3. Group 4: Donepezil-treated AD-group: rats were given Donepezil 5 mg/kg orally for 8 weeks and for the last 4 weeks were injected AlCl3. Group 5: ATR 1 blocker-donepezil treated AD group. After the 8 weeks, animals were suspected to short term memory testing using the Novel Object Recognition test interpreting the discrimination index (DI), Recognition index (RI), frequency of exploration and locomotor activity. Malondialdehyde (MDA), Glutathione (GSH) and glutamate contents of cerebral cortex and hippocampus homogenates were biochemically assayed.Results: AlCl 3 -treated group showed impaired short-term memory indices and locomotor activity with increased MDA and decreased GSH as well as glutamate content in cerebral cortex and hippocampus. ATR 1 blocker-treated group showed significant improvement in memory function, decreased MDA and increased GSH as well as decreased glutamate content. In ATR 1 blocker plus donepezil -treated group the effects of both drugs were additive and parallel.Conclusion: ATR 1 blockade improved memory function in ATD induced by AlCl 3 injection in rats and exerts antioxidant and antiexcitotoxic effects.