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Subject Area

Clinical Pharmacology

Article Type

Original Study

Abstract

Objective This study aimed to investigate the antiamnestic effect of losartan and/or donepezil in a l-methionine model of vascular dementia (VaD). Background VaD is a major public health problem worldwide. It is the second most common cause of dementia after Alzheimer disease. Combination therapy involving an acetylcholinesterase inhibitor with other neuroprotective agents has shown better desirable effects in the prevention of dementia. Materials and Methods Rats were divided into five groups treated for 4 weeks as follows: control group, l-methionine group, which received l-methionine 1.7 g/kg/day orally to induce VaD, donepezil group, which received donepezil 2.5 mg/kg/day in addition to l-methionine, losartan group, which received losartan 2.25 mg/kg/day in addition to l-methionine, and the combination group, which received both losartan 2.25 mg/kg/day and donepezil 2.5 mg/kg/day in addition to l-methionine. After 4 consecutive weeks of treatment, behavioral tests, biochemical parameters, and histopathological assessment of brain tissues were performed for all groups. Results Pretreatment with losartan and donepezil showed a significant increase in the number of crossed squares/5 min in the open-field test, a significant increase in the memory index in the novel object recognition test, a significant decrease in transfer latency in the elevated plus maze test, a significant decrease in serum malondialdehyde and a significant increase in serum glutathione-s-transferase, and nitric oxide. Improvements in histopathological changes of VaD were observed. Conclusion Donepezil and losartan may play a role in neuroprotection in l-methionine-induced VaD. Combined treatment showed better antiamnestic effect than either treatment alone.

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