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.

Alendronate reduces the cognitive and neurological disturbances induced by combined doses of d‐galactose and aluminum chloride in mice

“…Additionally, d ‐gal + AlCl 3 ‐administered mice showed decreased STL in PA test exhibiting a decline in nonspatial memory. Therefore, this decline in spatial and nonspatial learning and memory in mice after exposure to d ‐gal + AlCl 3 confirms the findings in previous similar reports (Jayant et al, 2016; Rani et al, 2015). Nevertheless, treatment of d ‐gal + AlCl 3 ‐exposed mice with ALN (1.76 mg/kg p.o.)…”

Amelioration of Aluminum- And Fluoride-Induced Behavioral Alterations Through Resveratrol in Rats.

“…In the present study, a marked decrease in bw and brain weight in aluminum and fluoride exposed animals was observed as compared to the control group animals. These findings are also in line with the previous studies done in other laboratories [18][19][20], and these changes were significantly reversed when resveratrol administered concomitantly with aluminum and fluoride. On the other hand, resveratrol alone given animal's body and brain weights were very nearer to the control group animal's weight.…”

Intracellular Calcium Dysregulation: Implications for Alzheimer’s Disease

“…Interestingly, Morris water maze test, plus maze test and different biochemical analysis, demonstrated the restoration of normal learning and memory functions. Moreover, SCR-1693 (a nonselective calcium channel blocker) has been described to attenuate A β 25–35 -induced death in SH-SY5Y cells and to regulate A β -induced signal cascade in neurons [ 58 – 60 ]. However, the use of calcium channel blockers to mitigate AD outcomes is still much debated.…”