In vivo study of dose-dependent antioxidant efficacy of functionalized core\u2013shell yttrium oxide nanoparticles

Samr Kassem,Mahmoud M Arafa,Manal M Yehya,Mostafa A M Soliman

doi:10.1007/s00210-022-02219-1

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

Highlights

The production of free radicals (ROS and RNS) surpasses the antioxidant systems’ ability to detoxify the generated reactive intermediates or repair cellular damage, resulting in oxidative stress (Di Meo et al 2016; Zhang et al 2016a, b, c)
Oxidative stress was successfully induced in all experimental groups (1, 2, and 3) by daily exposure to different temperature degrees (35–40 °C) for 6 h per day and (15–20 °C) for 6 h per night for 1 week compared with control one (Fig. 1A–C) and supplementary file 4
ethylene glycol methacrylate phosphate (EGMP) yttrium oxide nanoparticles (YNPs) able to pass through the blood–brain barrier (BBB) which is approved by fluorescence and transmission electron microscope (TEM) imaging and help in rescuing the different cells from oxidative stress–related damage

Summary

Introduction

The production of free radicals (ROS and RNS) surpasses the antioxidant systems’ ability to detoxify the generated reactive intermediates or repair cellular damage, resulting in oxidative stress (Di Meo et al 2016; Zhang et al 2016a, b, c). The generation of reactive oxygen species (ROS) during oxidative stress is critical for signal transduction and homeostasis (Ray et al 2012). Naunyn-Schmiedeberg's Archives of Pharmacology generation is a normal cellular function that is associated with various signaling pathways as well as the immune system’s defense mechanism. Superoxide anion (O2∙−), hydroxyl radical (OH∙), hydrogen peroxide (H2O2), singlet oxygen (1O2), and hypochlorous acid (HOCL) are all forms of reactive oxygen species (ROS). Following the reduction of oxygen, either H2O2 is formed via dismutation or OH∙ is generated via the Fenton reaction (Thannickal and Fanburg 2002)

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