Adv Pharm Bull. 2016;6(4):531-539 doi: 10.15171/apb.2016.067
Captopril and Valsartan May
Improve Cognitive Function Through Potentiation of the Brain Antioxidant
Defense System and Attenuation of Oxidative/Nitrosative Damage in STZ-Induced
Dementia in Rat
Purpose: Previous findings have shown the crucial roles of brain
renin-angiotensin system (RAS) in pathogenesis of Alzheimer’s disease (AD).
Since RAS inhibitors may have beneficial effects on dementia and cognitive
function in elderly people, the aim of present study was to examine the
neuroprotective actions of captopril and valsartan on memory function and
neuronal damage in experimental model of AD.
Methods: Adult forty male Wistar rats (220-280g)
were randomly divided into 5 groups; Control, Vehicle, Alzheimer and treatment
groups. AD was induced by the injections of streptozotocin (3mg/kg, bilateral
intracerebroventricular) at days 1&3. Treated rats received orally
captopril (50mg/kg/day) and valsartan (30mg/kg/day). Memory function and
histological assessments were done at termination of experiment. Finally,
superoxide dismutase (SOD) and catalase (CAT) activities as well as
malondialdehyde (MDA) and NOx contents were determined.
Results: There was a significant increase in the
mean value of latency in Alzheimer group (66%). Captopril and valsartan
considerably decreased this value in both treatment groups (45% and 72%,
respectively). In Alzheimer group the activities of brain’s SOD and CAT reduced
(40% and 47%, respectively) in accompany with an increase in MDA and NOx
contents (49% and 50%, respectively). Captopril and valsartan significantly
increased the activities of brain’s SOD and CAT concomitant reduction in MDA
and NOx contents. Also, histopathological damages noticeably decreased
in both treatment groups.
Conclusion: Our findings indicate that RAS inhibition
by using captopril and valsartan potentiates the antioxidant defense system of
brain and reduces oxidative/nitrosative stress in accompany with neuronal
damage during AD.