title: Zinc Modulates Nanosilver-Induced Toxicity in Primary Neuronal Cultures.
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 ZnCl(2), respectively. Elimination of zinc leads to complete death of nanosilver-treated CGCs. In contrast, supplementation with ZnCl(2) 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.
authors.affiliation: Laboratory of Pharmaconeurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego str, 02-106, Warsaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Ziemińska
authors.affiliation: Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego str, 02-106, Warsaw, Poland. lidkas@imdik.pan.pl.
authors.forename: Lidia
authors.initials: L
authors.lastname: Strużyńska
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D005029:Ethylenediamines / Q000494:pharmacology; D005260:Female; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D010316:Particle Size; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000633:toxicity*; D015032:Zinc / Q000032:analysis* / Q000494:pharmacology*
chemical_list: D002614:Chelating Agents; D005029:Ethylenediamines; D017382:Reactive Oxygen Species; D012834:Silver; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; D002118:Calcium
keywords: Cell death; Free radicals; NMDA receptor; Nanotoxicity; TPEN; Zinc homeostasis