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Vitamin D alleviates cognitive dysfunction and brain damage induced by copper sulfate intake in experimental rats: focus on its combination with donepezil
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Vitamin D alleviates cognitive dysfunction and brain damage induced by copper sulfate intake in experimental rats: focus on its combination with donepezil
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Journal Article
Vitamin D alleviates cognitive dysfunction and brain damage induced by copper sulfate intake in experimental rats: focus on its combination with donepezil
2023
Overview
This study aimed to demonstrate the potential benefits of donepezil (DPZ) and vitamin D (Vit D) in combination to counteract the neurodegenerative disorders induced by CuSO
intake in experimental rats. Neurodegeneration (Alzheimer-like) was induced in twenty-four male Wistar albino rats by CuSO
supplement to drinking water (10 mg/L) for 14 weeks. AD rats were divided into four groups: untreated AD group (Cu-AD) and three treated AD groups; orally treated for 4 weeks with either DPZ (10 mg/kg/day), Vit D (500 IU/kg/day), or DPZ + Vit D starting from the 10th week of CuSO
intake. Another six rats were used as normal control (NC) group. The hippocampal tissue content of β-amyloid precursor protein cleaving enzyme 1 (BACE1), phosphorylated Tau (p-tau), clusterin (CLU), tumor necrosis factor-α (TNF-α), caspase-9 (CAS-9), Bax, and Bcl-2 and the cortical content of acetylcholine (Ach), acetylcholinesterase (AChE), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured. Cognitive function tests (Y-maze) and histopathology studies (hematoxylin and eosin and Congo red stains) and immunohistochemistry for neurofilament. Vit D supplementation alleviated CuSO
-induced memory deficits including significant reduction hippocampal BACE1, p-tau, CLU, CAS-9, Bax, and TNF-α and cortical AChE and MDA. Vit D remarkably increased cortical Ach, TAC, and hippocampal Bcl-2. It also improved neurobehavioral and histological abnormalities. The effects attained by Vit D treatment were better than those attained by DPZ. Furthermore, Vit D boosted the therapeutic potential of DPZ in almost all AD associated behavioral and pathological changes. Vit D is suggested as a potential therapy to retard neurodegeneration.
Publisher
Springer Berlin Heidelberg
Subject
Acetylcholinesterase - metabolism
/ Alzheimer Disease - chemically induced
/ Alzheimer Disease - drug therapy
/ Alzheimer Disease - metabolism
/ Amyloid Precursor Protein Secretases - metabolism
/ Amyloid Precursor Protein Secretases - pharmacology
/ Amyloid Precursor Protein Secretases - therapeutic use
/ Animals
/ Antioxidants - therapeutic use
/ Aspartic Acid Endopeptidases - metabolism
/ Aspartic Acid Endopeptidases - pharmacology
/ Aspartic Acid Endopeptidases - therapeutic use
/ bcl-2-Associated X Protein - metabolism
/ Brain
/ Cognitive Dysfunction - chemically induced
/ Copper
/ Copper Sulfate - adverse effects
/ Male
/ Rats
