Coating-Dependent Neurotoxicity of Silver Nanoparticles—An In Vivo Study on Hippocampal Oxidative Stress and Neurosteroids

Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials. The level of exposure to nanosilver is constantly raising, and a growing body of research highlights that it is harmful to the health, especially the nervous system, of humans. The potential pathways through which nanosilver...

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Main Authors: Katarzyna Dziendzikowska, Jacek Wilczak, Wojciech Grodzicki, Joanna Gromadzka-Ostrowska, Małgorzata Węsierska, Marcin Kruszewski
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/3/1365
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author Katarzyna Dziendzikowska
Jacek Wilczak
Wojciech Grodzicki
Joanna Gromadzka-Ostrowska
Małgorzata Węsierska
Marcin Kruszewski
author_facet Katarzyna Dziendzikowska
Jacek Wilczak
Wojciech Grodzicki
Joanna Gromadzka-Ostrowska
Małgorzata Węsierska
Marcin Kruszewski
author_sort Katarzyna Dziendzikowska
collection DOAJ
description Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials. The level of exposure to nanosilver is constantly raising, and a growing body of research highlights that it is harmful to the health, especially the nervous system, of humans. The potential pathways through which nanosilver affects neurons include the release of silver ions and the associated induction of oxidative stress. To better understand the mechanisms underlying the neurotoxicity of nanosilver, in this study we exposed male Wistar rats to 0.5 mg/kg body weight of AgNPs coated with bovine serum albumin (BSA), polyethylene glycol (PEG), or citrate, or to AgNO<sub>3</sub> as a source of silver ions for 28 days and assessed the expression of antioxidant defense markers in the hippocampus of the exposed animals after 1 week of spatial memory training. We also evaluated the influence of AgNPs coating on neurosteroidogenesis in the rat hippocampus. The results showed that AgNPs disrupted the antioxidant system in the hippocampus and induced oxidative stress in a coating-dependent manner, which could potentially be responsible for neurodegeneration and cognitive disorders. The analysis of the influence of AgNPs on neurosteroids also indicated coating-dependent modulation of steroid levels with a significant decrease in the concentrations of progesterone and 17α-progesterone in AgNPs(BSA), AgNPs(PEG), and Ag<sup>+</sup> groups. Furthermore, exposure to AgNPs or Ag<sup>+</sup> resulted in the downregulation of selected genes involved in antioxidant defense (<i>Cat</i>), neurosteroid synthesis (<i>Star</i>, <i>Hsd3b3</i>, <i>Hsd17b1</i>, and <i>Hsd17b10</i>), and steroid metabolism (<i>Ar</i>, <i>Er1</i>, and <i>Er2</i>). In conclusion, depending on the coating material used for their stabilization, AgNPs induced oxidative stress and modulated the concentrations of steroids as well as the expression of genes involved in steroid synthesis and metabolism.
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spelling doaj.art-f8cba28dde5342119abb3b1314cb6f8e2023-11-23T16:39:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-01233136510.3390/ijms23031365Coating-Dependent Neurotoxicity of Silver Nanoparticles—An In Vivo Study on Hippocampal Oxidative Stress and NeurosteroidsKatarzyna Dziendzikowska0Jacek Wilczak1Wojciech Grodzicki2Joanna Gromadzka-Ostrowska3Małgorzata Węsierska4Marcin Kruszewski5Department of Dietetics, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences—SGGW, Nowoursynowska 159C, 02-776 Warsaw, PolandDepartment of Physiological Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159, 02-776 Warsaw, PolandDepartment of Dietetics, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences—SGGW, Nowoursynowska 159C, 02-776 Warsaw, PolandDepartment of Dietetics, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences—SGGW, Nowoursynowska 159C, 02-776 Warsaw, PolandLaboratory of Neuropsychology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, PolandCentre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, PolandSilver nanoparticles (AgNPs) are one of the most widely used nanomaterials. The level of exposure to nanosilver is constantly raising, and a growing body of research highlights that it is harmful to the health, especially the nervous system, of humans. The potential pathways through which nanosilver affects neurons include the release of silver ions and the associated induction of oxidative stress. To better understand the mechanisms underlying the neurotoxicity of nanosilver, in this study we exposed male Wistar rats to 0.5 mg/kg body weight of AgNPs coated with bovine serum albumin (BSA), polyethylene glycol (PEG), or citrate, or to AgNO<sub>3</sub> as a source of silver ions for 28 days and assessed the expression of antioxidant defense markers in the hippocampus of the exposed animals after 1 week of spatial memory training. We also evaluated the influence of AgNPs coating on neurosteroidogenesis in the rat hippocampus. The results showed that AgNPs disrupted the antioxidant system in the hippocampus and induced oxidative stress in a coating-dependent manner, which could potentially be responsible for neurodegeneration and cognitive disorders. The analysis of the influence of AgNPs on neurosteroids also indicated coating-dependent modulation of steroid levels with a significant decrease in the concentrations of progesterone and 17α-progesterone in AgNPs(BSA), AgNPs(PEG), and Ag<sup>+</sup> groups. Furthermore, exposure to AgNPs or Ag<sup>+</sup> resulted in the downregulation of selected genes involved in antioxidant defense (<i>Cat</i>), neurosteroid synthesis (<i>Star</i>, <i>Hsd3b3</i>, <i>Hsd17b1</i>, and <i>Hsd17b10</i>), and steroid metabolism (<i>Ar</i>, <i>Er1</i>, and <i>Er2</i>). In conclusion, depending on the coating material used for their stabilization, AgNPs induced oxidative stress and modulated the concentrations of steroids as well as the expression of genes involved in steroid synthesis and metabolism.https://www.mdpi.com/1422-0067/23/3/1365silver nanoparticlesnanoparticle coatinghippocampusneurosteroidsoxidative stressantioxidative defense
spellingShingle Katarzyna Dziendzikowska
Jacek Wilczak
Wojciech Grodzicki
Joanna Gromadzka-Ostrowska
Małgorzata Węsierska
Marcin Kruszewski
Coating-Dependent Neurotoxicity of Silver Nanoparticles—An In Vivo Study on Hippocampal Oxidative Stress and Neurosteroids
International Journal of Molecular Sciences
silver nanoparticles
nanoparticle coating
hippocampus
neurosteroids
oxidative stress
antioxidative defense
title Coating-Dependent Neurotoxicity of Silver Nanoparticles—An In Vivo Study on Hippocampal Oxidative Stress and Neurosteroids
title_full Coating-Dependent Neurotoxicity of Silver Nanoparticles—An In Vivo Study on Hippocampal Oxidative Stress and Neurosteroids
title_fullStr Coating-Dependent Neurotoxicity of Silver Nanoparticles—An In Vivo Study on Hippocampal Oxidative Stress and Neurosteroids
title_full_unstemmed Coating-Dependent Neurotoxicity of Silver Nanoparticles—An In Vivo Study on Hippocampal Oxidative Stress and Neurosteroids
title_short Coating-Dependent Neurotoxicity of Silver Nanoparticles—An In Vivo Study on Hippocampal Oxidative Stress and Neurosteroids
title_sort coating dependent neurotoxicity of silver nanoparticles an in vivo study on hippocampal oxidative stress and neurosteroids
topic silver nanoparticles
nanoparticle coating
hippocampus
neurosteroids
oxidative stress
antioxidative defense
url https://www.mdpi.com/1422-0067/23/3/1365
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