title: Protective effect of a calcium channel blocker "diltiazem" on aluminum chloride-induced dementia in mice.
abstract: Many studies report that heavy metals such as aluminum are involved in amyloid beta aggregation and neurotoxicity. Further, high concentration of aluminum in the brain deregulates calcium signaling which contributes to synaptic dysfunction and halts neuronal communication which ultimately leads to the development of Alzheimer's disease. Recently, diltiazem, a calcium channel blocker clinically used in angina, is reported to decrease amyloid beta production by inhibiting calcium influx, decreasing inflammation and oxidative stress. However, the probable role of this drug in aluminum chloride (AlCl3)-induced experimental dementia is yet to be explored. Therefore, the present study is designed to investigate the effect of AlCl3-induced dementia in mice. Morris water maze test and elevated plus maze were utilized to evaluate learning and memory. Various biochemical estimations including brain acetylcholinesterase activity (AChE), brain total protein, thiobarbituric acid-reactive species (TBARS) level, reduced glutathione (GSH) level, nitrate/nitrite, and superoxide dismutase (SOD) were measured. AlCl3 significantly impaired learning and memory and increased brain AChE, brain total protein, TBARS, and nitrate/nitrite and decreased brain GSH or SOD. On the other hand, treatment with diltiazem significantly reversed AlCl3-induced behavioral and biochemical deficits. The present study indicates the beneficial role of diltiazem in AlCl3-induced dementia.
authors.affiliation: Pharmacology Research Lab, Department of Pharmacology, Chandigarh College of Pharmacy, Landran, Mohali, Punjab, 140307, India. anusheoran99@gmail.com.
authors.forename: Anu
authors.initials: A
authors.lastname: Rani
authors.affiliation: Department of Pharmacology, Chandigarh College of Pharmacy, Landran, Mohali, Punjab, 140307, India. cgc.ccp.na@gmail.com.
authors.identifier: http://orcid.org/0000-0002-0759-584X
authors.lastname: Neha
authors.affiliation: Department of Pharmacology, Chandigarh College of Pharmacy, Landran, Mohali, Punjab, 140307, India. itsrupinder@yahoo.com.
authors.forename: Rupinder K
authors.initials: RK
authors.lastname: Sodhi
authors.affiliation: Pharmacology Research Lab, Department of Pharmacology, Chandigarh College of Pharmacy, Landran, Mohali, Punjab, 140307, India. amanrai600@gmail.com.
authors.forename: Amanpreet
authors.initials: A
authors.lastname: Kaur
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D002712:Chlorides; D003704:Dementia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004110:Diltiazem / Q000627:therapeutic use*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009573:Nitrites / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D017607:Aluminum Compounds; D002121:Calcium Channel Blockers; D002712:Chlorides; D018696:Neuroprotective Agents; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; D000077410:Aluminum Chloride; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase; D004110:Diltiazem; D005978:Glutathione
keywords: Aluminum chloride; Dementia; Diltiazem; Morris water maze; Oxidative stress