Ceria Nanoparticles Decrease UVA-Induced Fibroblast Death Through Cell Redox Regulation Leading to Cell Survival, Migration and Proliferation.

Fabianne Martins Ribeiro,Sushant Singh,Craig J Neal,Celso Vataru Nakamura,Sudipta Seal,Tamil S Sakthivel,Tânia Ueda-Nakamura,Sueli De Oliveira Silva Lautenschlager,Mariana Maciel De Oliveira

doi:10.3389/fbioe.2020.577557

Abstract

Exposure to ultraviolet radiation is a major contributor to premature skin aging and carcinogenesis, which is mainly driven by overproduction of reactive oxygen species (ROS). There is growing interest for research on new strategies that address photoaging prevention, such as the use of nanomaterials. Cerium oxide nanoparticles (nanoceria) show enzyme-like activity in scavenging ROS. Herein, our goal was to study whether under ultraviolet A rays (UVA)-induced oxidative redox imbalance, a low dose of nanoceria induces protective effects on cell survival, migration, and proliferation. Fibroblasts cells (L929) were pretreated with nanoceria (100 nM) and exposed to UVA radiation. Pretreatment of cells with nanoceria showed negligible cytotoxicity and protected cells from UVA-induced death. Nanoceria also inhibited ROS production immediately after irradiation and for up to 48 h and restored the superoxide dismutase (SOD) activity and GSH level. Additionally, the nanoceria pretreatment prevented apoptosis by decreasing Caspase 3/7 levels and the loss of mitochondrial membrane potential. Nanoceria significantly improved the cell survival migration and increased proliferation, over a 5 days period, as compared with UVA-irradiated cells, in wound healing assay. Furthermore, it was observed that nanoceria decreased cellular aging and ERK 1/2 phosphorylation. Our study suggests that nanoceria might be a potential ally to endogenous, antioxidant enzymes, and enhancing the redox potentials to fight against UVA-induced photodamage and consequently modulating the cells survival, migration, and proliferation.

Highlights

Nanotechnology has attracted tremendous attention in different fields of science including medicine and pharmacology
The current study extends the findings of another study on the photo-protective effects of nanoceria toward fibroblasts and keratinocytes (Caputo et al, 2015; Li et al, 2019)
High doses of ultraviolet A rays (UVA) were utilized and the changes to antioxidant/reactive oxygen species (ROS) activity and cell survival were monitored over several days, post-irradiation

Summary

Introduction

Nanotechnology has attracted tremendous attention in different fields of science including medicine and pharmacology. Cerium exists in a mixed valence state (Ce3+ and Ce4+) as an oxide and, due to the relatively low redox potential between these states, allows CNPs to have self-regenerative redox cycling properties, upon release or uptake of oxygen (termed oxygen buffering or oxygen storage capacity). This redox cycling, and interaction with the surrounding chemical environment, is evidenced practically as catalase (CAT) and superoxide dismutase (SOD)-mimetic activities. Other studies have demonstrated indirect effects of nanoceria treatment on ROS levels as modulations in native antioxidant enzyme concentrations (e.g., SOD2, glutathione) (Das et al, 2018) as well as expression of proteins related to cellular oxygen metabolism (e.g., HIF1α) (Das et al, 2012)

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