Effect of Colloidal Aqueous Solution of Fullerene (C60) in the Presence of a P-Glycoprotein Inhibitor (Verapamil) on Spatial Memory and Hippocampal Expression of Sirtuin6, SELADIN1, and AQP1 Genes in a Rat Model of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most common types of neurodegenerative diseases which is accompanied by irreversible neuronal damage, learning difficulties, memory impairments, and cognitive disorders. The cholinergic system is destroyed during AD pathogenesis, leading to the major symptoms of the disease. Although in severe stages AD is life threatening, to date no absolute treatment has been found for this illness and some palliative options 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 to further compare the results with that of donepezil (DNPZL) as a standard drug. FAS was prepared via a solvent exchange method. The particle size was in the 119.14 ± 3.38 nm range with polydispersity index of 0.15 ± 0.02 and 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 the C60 concentration in FAS (21 μg/mL). Efficiencies of drugs were examined in both pretreatment and post-treatment groups of animals to better understand how they participate in affecting AD symptoms. Seeing that previous studies have presented antithetical declarations about whether C60 is a P-glycoprotein (P-gp) substrate, we studied FAS effects in both conditions of the presence and absence of a P-gp inhibitor (verapamil HCl, 25 mg/kg). In order to clarify the molecular mechanisms of action of two drugs, their effects on the expression 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 for improving AD symptoms, especially memory impairment, and further assert that more studies are needed to elucidate C60 and P-gp interaction type.