Attenuating effect of lisinopril and telmisartan in intracerebroventricular streptozotocin induced experimental dementia of Alzheimer's disease type: possible involvement of PPAR-γ agonistic property.
This study investigates the beneficial role of lisinopril, an angiotensin converting enzyme inhibitor (ACEI) and telmisartan, an angiotensin receptor blocker (ARB), in intracerebroventricular (i.c.v.) streptozotocin (STZ) induced dementia of Alzheimer's disease (AD) type in mice. This study also aimed to explore the role of PPAR-γ in lisinopril and telmisartan mediated effects in i.c.v. STZ mice. Donepezil served as the positive control in the study. Mice underwent i.c.v. injection of STZ. The Morris water maze (MWM) test was employed for assessment of learning and memory. Various biochemical estimations, namely brain acetylcholinesterase (AChE) activity, myeloperoxidase (MPO) activity, nitrite/nitrate and thiobarbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels, were also performed. The study showed that i.c.v. STZ significantly impaired learning and memory of the animals along with a significant enhancement in brain AChE, MPO, TBARS, nitrite/nitrate levels and reduction in brain GSH levels. Treatments of lisinopril/telmisartan/donepezil significantly attenuated STZ induced behavioral and biochemical changes. Pre-treatment with bisphenol-A-diglycidyl ether (BADGE), a selective PPAR-γ antagonist, significantly abolished the beneficial effect of lisinopril/telmisartan in i.c.v. STZ treated animals. The results of this investigation document a potential role of PPAR-γ in the beneficial effects of lisinopril and telmisartan in i.c.v. STZ dementia of AD type.
Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, India.
Birdavinder
B
Singh
Bhupesh
B
Sharma
Amteshwar S
AS
Jaggi
Nirmal
N
Singh
D000544:Alzheimer Disease / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D003224:Congo Red / Q000378:metabolism; D003704:Dementia / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D007276:Injections, Intraventricular; D017706:Lisinopril / Q000494:pharmacology / Q000627:therapeutic use*; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects; D013194:Staining and Labeling; D013311:Streptozocin; D000077333:Telmisartan
D001562:Benzimidazoles; D001565:Benzoates; D047495:PPAR gamma; D003224:Congo Red; D013311:Streptozocin; D017706:Lisinopril; D000077333:Telmisartan