Zinc Modulates Nanosilver-Induced Toxicity in Primary Neuronal Cultures.

Elżbieta Ziemińska,Lidia Strużyńska

doi:10.1007/s12640-015-9583-3

Elżbieta Ziemińska, Lidia Strużyńska

Open Access

https://doi.org/10.1007/s12640-015-9583-3

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Abstract

Silver nanoparticles (NAg) have recently become one of the most commonly used nanomaterials. Since the ability of nanosilver to enter the brain has been confirmed, there has been a need to investigate mechanisms of its neurotoxicity. We previously showed that primary neuronal cultures treated with nanosilver undergo destabilization of calcium homeostasis via a mechanism involving glutamatergic NMDA receptors. Considering the fact that zinc interacts with these receptors, the aim of the present study was to examine the role of zinc in mechanisms of neuronal cell death in primary cultures. In cells treated with nanosilver, we noted an imbalance between extracellular and intracellular zinc levels. Thus, the influence of zinc deficiency and supplementation on nanosilver-evoked cytotoxicity was investigated by treatment with TPEN (a chelator of zinc ions), or ZnCl2, respectively. Elimination of zinc leads to complete death of nanosilver-treated CGCs. In contrast, supplementation with ZnCl2 increases viability of CGCs in a dose-dependent manner. Addition of zinc provided protection against the extra/intracellular calcium imbalance in a manner similar to MK-801, an antagonist of NMDA receptors. Zinc chelation by TPEN decreases the mitochondrial potential and dramatically increases the rate of production of reactive oxygen species. Our results indicate that zinc supplementation positively influences nanosilver-evoked changes in CGCs. This is presumed to be due to an inhibitory effect on NMDA-sensitive calcium channels.

Highlights

In recent years, silver nanoparticles (NAg) have become an extremely popular nanotechnology product widely used in many applications
We have previously investigated the mechanisms of cell death in cultured cerebellar granule cells (CGC) exposed to silver nanoparticles (Zieminska et al 2014)
The results of this study indicated that overactivation of glutamatergic Nmethyl-D-aspartate receptors (NMDARs) is involved in neuronal cell death via excessive entry of calcium ions followed by an intracellular calcium imbalance

Summary

Introduction

Silver nanoparticles (NAg) have become an extremely popular nanotechnology product widely used in many applications. Their strong antibacterial potential is Neurotox Res (2016) 29:325–343 useful in medical products (Samuel and Gugenbichler 2004; Zheng et al, 2010) and they are found in a growth market of consumer articles (for review see: Schluesener and Schluesener 2013). It has been reported that nanosilver has an influence on mitochondrial function, generation of free radicals (AshaRani et al 2009; Hussain et al 2005; Singh and Ramarao 2012) and induction of apoptosis due to lowering of the cellular antioxidant glutathione (Piao et al 2011). Since NAg have been shown to enter the brain by permeating the blood– brain barrier (BBB) (Hoet et al 2004; Sharma et al 2009) and significantly accumulate in this organ, it is important to clarified their neurotoxic effects

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