Defensive effect of lansoprazole in dementia of AD type in mice exposed to streptozotocin and cholesterol enriched diet.
The present study investigates the potential of lansoprazole (a proton pump inhibitor and agonist of liver x receptors) in experimental dementia of AD type. Streptozotocin [STZ, 3 mg/kg, injected intracerebroventricular (i.c.v), and high fat diet (HFD, administered for 90 days)] were used to induce dementia in separate groups of Swiss mice. Morris water maze (MWM) test was performed to assess learning and memory of the animals. A battery of biochemical and histopathological studies were also performed. Extent of oxidative stress was measured by estimating the levels of brain reduced glutathione (GSH) and thiobarbituric acid reactive species (TBARS). Brain acetylcholinestrase (AChE) activity and serum cholesterol levels were also estimated. The brain level of myeloperoxidase (MPO) was measured as a marker of inflammation. STZ and HFD produced a marked decline in MWM performance of the animals, reflecting impairment of learning and memory. STZ/HFD treated mice exhibited a marked accentuation of AChE activity, TBARS and MPO levels along with a fall in GSH levels. Further, the stained micrographs of STZ/HFD treated mice indicated pathological changes, severe neutrophilic infiltration and amyloid deposition. Lansoprazole treatment significantly attenuated STZ and HFD -induced memory deficits, biochemical and histopathological alterations. It also prevented HFD-induced rise in the cholesterol level. Therefore, the findings demonstrate potential of lansoprazole in memory dysfunctions which may probably be attributed to its anti-cholinesterase, anti-oxidative and anti-inflammatory effects. Moreover, both cholesterol-dependent as well as cholesterol-independent effects of lansoprazole appear to play a role. In addition study indicates the role of liver x receptors in dementia.
Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Punjab, India.
Rupinder K
RK
Sodhi
Nirmal
N
Singh
D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000009:adverse effects; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007276:Injections, Intraventricular; D064747:Lansoprazole / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009195:Peroxidase / Q000378:metabolism; D054328:Proton Pump Inhibitors / Q000494:pharmacology; D013311:Streptozocin / Q000008:administration & dosage / Q000633:toxicity; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D002791:Cholesterol, Dietary; D054328:Proton Pump Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; D064747:Lansoprazole; D013311:Streptozocin; D002784:Cholesterol; D009195:Peroxidase; D000110:Acetylcholinesterase; D005978:Glutathione