Exploitation of HIV protease inhibitor Indinavir as a memory restorative agent in experimental dementia.
The present study was undertaken to investigate the beneficial effect of HIV protease inhibitor Indinavir on memory deficits associated with experimental dementia of Alzheimer disease's (AD) type. Dementia was induced in Swiss albino mice by administration of Celecoxib (100 mg kg(-1) orally, daily for 9 days) or Streptozotocin (3 mg kg(-1) administered intracerebroventricularly on 1st and 3rd day) and the cognitive behaviors of Swiss albino mice were assessed using Morris water maze test. Brain acetyl cholinesterase (AChE) activity was measured by Ell Mann's method. Brain thiobarbituric acid reactive species (TBARS) levels and reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method respectively to assess total oxidative stress. Donepezil (0.1 mg kg(-1) i.p.) served as positive control in the present investigation. Celecoxib as well as Streptozotocin (STZ) produced a significant loss of learning and memory. Indinavir (100 and 200 mg kg(-1) orally) successfully attenuated Celecoxib as well as STZ induced cognitive deficits. Higher levels of brain AChE activity, TBARS and lower levels of GSH were observed in Celecoxib as well as STZ treated animals, which were significantly attenuated by Donepezil and Indinavir. Study highlights the potential of Indinavir in memory dysfunctions associated with dementia of AD.
Sharma
Bhupesh
B
Pharmacology Division, Department of Pharmaceutical Sciences & Drug Research, Punjabi University, Patiala (Punjab), India. bhupeshresearch@gmail.com
Singh
Nirmal
N
Singh
Manjeet
M
Jaggi
Amteshwar Singh
AS
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity; D003704:Dementia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D000077265:Donepezil; D005260:Female; D005978:Glutathione / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D007189:Indans / Q000494:pharmacology; D019469:Indinavir / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D051379:Mice; D018697:Nootropic Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000633:toxicity; D013311:Streptozocin / Q000633:toxicity; D013449:Sulfonamides / Q000633:toxicity; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D016861:Cyclooxygenase Inhibitors; D017320:HIV Protease Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D011720:Pyrazoles; D013449:Sulfonamides; D017392:Thiobarbituric Acid Reactive Substances; D013311:Streptozocin; D019469:Indinavir; D000077265:Donepezil; D000110:Acetylcholinesterase; D005978:Glutathione; D000068579:Celecoxib