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The effect of colloidal aqueous solution of fullerene (C60) in the presence of a Pglycoprotein inhibitor (verapamil) on spatial memory and hippocampal expression of Sirtuin6, SELADIN1 and AQP1 genes in rat model of Alzheimer’s disease
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Mehrnoosh Nikpour   |
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Abstract: (190 Views) |
Introduction: Alzheimer’s disease (AD) is one of the most common types of neurodegenerative diseases which is along with irreversible neuronal damages, learning difficulties, memory impairments and cognitive disorders. Cholinergic system is destroyed during AD pathogenesis and it also causes the major symptoms of the disease. Although in severe stages AD would be life threatening, but to date no absolute treatment has been found for this illness and just some palliating ways are available. The aim of this study was to investigate the effect of fullerene (C60) aqueous suspension (FAS) on improving spatial memory in amnesic male Wistar rats (weighing 200±20 g), and further compare the results with that of donepezil (DNPZL) as a standard drug. FAS was prepared via solvent exchange method. The particle size was in 119.14±3.38 nm range with PDI 0.15±0.02 and the zeta potential of -12.22±5.98 mV. A simple and high sensitive reversed phase high performance liquid chromatography (HPLC) method was developed to identify C60 concentration in FAS (21 µg/ml). Efficiencies of drugs were examined both in pre-treatment and post-treatment groups of animals to better understand how they participates in affecting AD symptoms. Seeing that previous studies have presented antithetical declarations about whether C60 is a P glycoprotein (P-gp) substrate or not, we studied FAS effects in both conditions of existence and absence of a P-gp inhibitor (verapamil HCl, 25 mg/kg). In order to clarify molecular mechanism of actions of two drugs, their effects on expressions of three principal genes, involved in AD including Sirtuin6, SELADIN1 and AQP1 and as well as their total antioxidant capacities (TACs), were studied. In order to induce memory impairment, scopolamine HBr (SCOP) was administered for 10 days (2 mg/kg/i.p).
FAS and DNPZL administration regimens were 21 µg/ml, BID (i.p.) and 10 mg/kg (p.o.) for 10 days respectively. Our results introduce FAS as a promising nanoformulation in improving AD symptoms, especially memory impairment, and further assert that more studies are needed to elucidate C60 and P-gp interaction type. |
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| Keywords: Alzheimer’s disease (AD), Fullerene (C60) aqueous suspension (FAS), Sirtuin6, SELADIN1, AQP1 |
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Full-Text [PDF 477 kb]
(27 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2024/03/3 | Accepted: 2023/08/10 | Published: 2023/08/10
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