Treatment of Human Lens Epithelium with High Levels of Nanoceria Leads to Reactive Oxygen Species Mediated Apoptosis.

Belal I Hanafy,Barbara Pierscionek,Gareth W V Cave,Yvonne Barnett

doi:10.3390/molecules25030441

Abstract

Nanoceria (cerium oxide nanoparticles) have been shown to protect human lens epithelial cells (HLECs) from oxidative stress when used at low concentrations. However, there is a lack of understanding about the mechanism of the cytotoxic and genotoxic effects of nanoceria when used at higher concentrations. Here, we investigated the impact of 24-hour exposure to nanoceria in HLECs. Nanoceria’s effects on basal reactive oxygen species (ROS), mitochondrial morphology, membrane potential, ATP, genotoxicity, caspase activation and apoptotic hallmarks were investigated. Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) studies on isolated mitochondria revealed significant uptake and localization of nanoceria in the mitochondria. At high nanoceria concentrations (400 µg mL−1), intracellular levels of ROS were increased and the HLECs exhibited classical hallmarks of apoptosis. These findings concur with the cells maintaining normal ATP levels necessary to execute the apoptotic process. These results highlight the need for nanoceria dose-effect studies on a range of cells and tissues to identify therapeutic concentrations in vitro or in vivo.

Highlights

Nanoparticles offer great potential as medical devices due to their unique physicochemical properties [1,2,3]
ethylene glycol coated nanoparticles (EGCNPs) were thoroughly characterized in our previous work using transmission electron microscopy, powder X-ray diffraction, dynamic light scattering, thermogravimetric analysis, gas chromatography-mass spectroscopy, Fourier transform infrared spectroscopy (FTIR), UV-Vis spectroscopy [20]
EGCNPs were monodisperse with unimodal distribution of intensity-weighted mean hydrodynamic diameters as was demonstrated by DLS [20]

Summary

Introduction

Nanoparticles offer great potential as medical devices due to their unique physicochemical properties [1,2,3]. Cerium oxide nanoparticles “nanoceria” are extensively researched for biomedical and drug delivery applications because of their unique recyclable antioxidant, neuroprotective, radioprotective and anti-inflammatory properties [4,5,6,7,8]. Nanoceria are increasingly used for industrial applications such as an additive to diesel fuel (commercially available under several trade names such as EnviroxTM) to reduce soot emissions and decrease fuel consumption [11,12]. This has led to increased exposure to nanoceria which warrants investigation of their toxicological effects and interactions with various eukaryotic cells. Nanoceria was considered a high priority for toxicological evaluation [12,13]

Methods

Results

Discussion

Conclusion