In vivo study of dose-dependent antioxidant efficacy of functionalized core–shell yttrium oxide nanoparticles

Abstract

Herein, we assess the dose-dependent antioxidant efficacy of ultrafine spherical functionalized core–shell yttrium oxide nanoparticles (YNPs) with a mean size of 7–8 nm and modified with poly EGMP (ethylene glycol methacrylate phosphate) and N-Fluorescein Acrylamide. The antioxidant properties of these nanoparticles were investigated in three groups of Sprague–Dawley rats (10 per group) exposed to environmental stress daily for 1 week and one control group. Groups 2 and 3 were intravenously injected twice a week with YNPs at 0.3 and 0.5 mg at 2nd and 5th day of environmental stress exposure respectively. Different samples of blood and serum were collected from all experimental groups at end of the experiment to measure oxidative biomarkers such as total antioxidant capacity (TAC), hydroxyl radical antioxidant capacity (HORAC), oxygen radical antioxidant capacity (ORAC), malondialdehyde (MDA), and oxidants concentration as hydrogen peroxide (H2O2). The liver, brain, and spleen tissues were collected for fluorescence imaging and histopathological examination in addition to brain tissue examination by transmission electron microscope (TEM). Inductively coupled plasma-mass spectrometry (ICP-MS) was used to estimate YNPs translocation and concentration in tissues which is consecutively dependent on the dose of administration. Depending on all results, poly EGMP YNPs (poly EGMP yttrium oxide nanoparticles) can act as a potent direct antioxidant in a dose-dependent manner with good permeability through blood–brain barrier (BBB). Also, the neuroprotective effect of YNPs opening the door to a new therapeutic approach for modulating oxidative stress–related neural disorders. Highlights • The dose-dependent antioxidant efficacy of ultrafine spherical functionalized core–shell yttrium oxide nanoparticles (YNPs) with a mean size of 7–8 nm and modified with poly EGMP (ethylene glycol methacrylate phosphate) and N-Fluorescein Acrylamide was assessed. • The dose of administration directly affecting the brain, liver, and spleen tissues distribution, retention, and uptake of YNPs and direct correlation between the absorbed amount and higher dose administered. • YNPs can act as a potent direct antioxidant in a dose-dependent manner with good permeability through blood–brain barrier (BBB). Graphical abstract

Alleviation of calcium hydroxide nanoparticles induced genotoxicity and gastritis by coadministration of calcium titanate and yttrium oxide nanoparticles in mice

“…Our findings of significant elevations in the gastric eNOS gene expression and non-noticeable changes in the gastric ROS level and expression level of inflammatory iNOS and COX-2 genes after coadministration of Ca(OH) 2 , CaTiO 3 and Y 2 O 3 nanoparticles revealed the absence of inflammation and oxidative stress and also confirmed the previously reported antioxidant and free radicals scavenging capacity of Y 2 O 3 nanoparticles because gastric eNOS overexpression decreases the formation of ROS and increases the expression of antioxidants such as superoxide dismutase and Heme-oxygenase-I 22 , 29 , 30 .…”

“…In contrast to the demonstrated Ca(OH) 2 nanoparticles induced genotoxicity, oral coadministration of CaTiO 3 and Y 2 O 3 nanoparticles simultaneously with Ca(OH) 2 nanoparticles was non-genotoxic and did not cause any noticeable changes in the integrity of gastric genomic DNA as detected by the non-significant changes observed in the measured DNA damage indicating parameters: tail length, %DNA in tail and tail moment after administration of Ca(OH) 2 , CaTiO 3 and Y 2 O 3 nanoparticles. Recently, Y 2 O 3 nanoparticles showed antioxidant capacity through scavenging free radicals, thus administration of Y 2 O 3 nanoparticles prohibits the induction of oxidative stress by decreasing the level of intracellular ROS generation and enhancing the antioxidant status of the cell 29 , 30 . Accordingly, the non-genotoxic effect detected after coadministration of CaTiO 3 and Y 2 O 3 nanoparticles simultaneously with Ca(OH) 2 nanoparticles may result from the antioxidant and free radicals scavenging abilities of Y 2 O 3 nanoparticles which prohibit Ca(OH) 2 nanoparticles induced ROS generation and DNA damage.…”

The effect of yttrium oxide nanoparticles on memory, inflammatory responses and mitochondrial biogenesis in cholestatic male Wistar rats

“…It has been observed in several studies that yttrium oxide nanoparticles can cross the blood-brain barrier, play their antioxidant roles, and protect cells that are exposed to oxidative stress (Panyala et al, 2019, Kassem et al, 2022. Also, yttrium oxide nanoparticles can reduce the level of ROS, improve the functions of mitochondria, prevent their fragmentation, and ultimately prevent hippocampal neuron apoptosis (Hosseini et al, 2015;Abu-Taweel et al, 2022).…”

Passing of Nanocarriers across the Histohematic Barriers: Current Approaches for Tumor Theranostics

“…The reduction of NP size makes it possible to implement both the paracellular pathway through tight junctions and passive transmembrane diffusion [ 135 ]. Various histohematic barriers are permeable for NPs with a size below approximately 10 nm for the BBB (e.g., yttrium oxide NPs [ 141 ], 2 nm [ 142 ], or 3 nm [ 143 ] AuNPs, polysiloxane NPs loaded with Gd chelate [ 144 ]), ~10–50 nm for the blood–brain tumor barrier (e.g., metallic NPs [ 145 ], NPs made of monomethoxy(polyethylene glycol)d,l-lactic-co-glycolic acid [ 146 ]), intestinal barrier (titanium dioxide NPs [ 147 ]) and blood–air barrier (e.g., fluorescent polystyrene nanospheres [ 148 ], AuNPs [ 16 ]), ~3 nm for glomerular barrier (e.g., AuNPs coated with glutathione [ 143 ], gold nanoclusters with a size less than 1 nm [ 149 ]) and blood–thymus barrier (nanoclusters of Mo132 and Mo 72 Fe 30 ). In the case of BBB permeation, the size decrease can not only promote drug delivery to the brain but also reduce drug uptake by the liver, thus decreasing drug toxicity [ 150 ].…”