Abstract
Background
Alzheimer's disease (AD) is a complex neurodegenerative disease. There is epidemiological evidence that heart failure (HF) patients are at higher risk of developing AD and the impact of sacubitril/valsartan, the first angiotensin receptor-neprilysin inhibitor (ARNI) approved for HF, on cognitive functions is still controversial.
Objective
To investigate the effect of sacubitril/valsartan on cognitive functions in colchicine-induced AD rat model.
Methods
Forty adult male Wistar rats were equally allocated into four groups (each of 10 rats). Group I: normal control, Group II: intracerebroventricular injection of colchicine (15μg/5μl/bilaterally), Group III: colchicine (15μg/5μl/bilaterally, icv) + oral sacubitril/valsartan (100 mg/kg/day) for 25 days and Group IV: colchicine (15μg/5μl/bilaterally, icv) + oral valsartan (50 mg/kg/day) for 25 days. Behavioral assessment was done using Morris water maze and passive avoidance tasks. Biochemically, β-amyloid (1-40 and 1-42) peptides, oxidative stress (malondialdehyde and superoxide dismutase) and inflammatory (tumor necrosis factor-alpha) parameters were measured in hippocampus and prefrontal cortex.
Results
Sacubitril/valsartan exaggerated colchicine-induced cognitive impairment in both Morris water maze and passive avoidance tasks, and was associated with significant increase in β-amyloid accumulation, oxidative stress and inflammation versus valsartan.
Conclusion
Sacubitril/valsartan caused deleterious effect on cognitive impairment and biochemical alterations in colchicine-induced AD rat model. Hence, special caution should be taken following long-term intake of ARNI on cognitive functions.
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