Acute toxicity and genotoxicity of silver nanoparticle in rats

The potential risk of a nanoparticle as a medical application has raised wide concerns, and this study aims to investigate silver nanoparticle (AgNP)-induced acute toxicities, genotoxicities, target organs and the underlying mechanisms. Sprague-Dawley rats were randomly divided into 4 groups (n = 4...

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Published inPloS one Vol. 12; no. 9; p. e0185554
Main Authors Wen, Hairuo, Dan, Mo, Yang, Ying, Lyu, Jianjun, Shao, Anliang, Cheng, Xiang, Chen, Liang, Xu, Liming
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 27.09.2017
Public Library of Science (PLoS)
Subjects
Aberration
Acute toxicity
Animal tissues
Animals
Archives & records
Biology and Life Sciences
Body weight
Bone marrow
Breakage
Carcinogens
Chronic toxicity
Damage
Deoxyribonucleic acid
DNA
Dosage
Drug dosages
Engineering and Technology
Female
Food
Gene expression
Genotoxicity
Heart
Hematology
Immune system
Irritation
Kidneys
Laboratories
Liver
Lungs
Medical equipment
Medical technology
Medicine and Health Sciences
Metal Nanoparticles - chemistry
Metal Nanoparticles - toxicity
Microscopy, Electron, Transmission
Mutagenicity Tests
Nanoparticles
Organs
Physiological aspects
Polyploidy
Rats
Rats, Sprague-Dawley
Rodents
Silver
Silver - chemistry
Spleen
Sucrose
Sugar
Thymus
Tissue Distribution
Toxicity
Toxicology
Transmission electron microscopy
China
Beijing China
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Abstract The potential risk of a nanoparticle as a medical application has raised wide concerns, and this study aims to investigate silver nanoparticle (AgNP)-induced acute toxicities, genotoxicities, target organs and the underlying mechanisms. Sprague-Dawley rats were randomly divided into 4 groups (n = 4 each group), and AgNP (containing Ag nanoparticles and released Ag+, 5 mg/kg), Ag+ (released from the same dose of AgNP, 0.0003 mg/kg), 5% sucrose solution (vechicle control) and cyclophophamide (positive control, 40 mg/kg) were administrated intravenously for 24 h respectively. Clinical signs and body weight of rats were recorded, and the tissues were subsequently collected for biochemical examination, Ag+ distribution detection, histopathological examination and genotoxicity assays. The rank of Ag detected in organs from highest to lowest is lung>spleen>liver>kidney>thymus>heart. Administration of AgNP induced a marked increase of ALT, BUN, TBil and Cre. Histopathological examination results showed that AgNP induced more extensive organ damages in liver, kidneys, thymus, and spleen. Bone marrow micronucleus assay found no statistical significance among groups (p > 0.05), but the number of aberration cells and multiple aberration cells were predominately increased from rats dosed with Ag+ and AgNP (p < 0.01), and more polyploidy cells were generated in the AgNP group (4.3%) compared with control. Our results indicated that the AgNP accumulated in the immune system organs, and mild irritation was observed in the thymus and spleen of animals treated with AgNP, but not with Ag+. The liver and kidneys could be the most affected organs by an acute i.v. dose of AgNP, and significantly increased chromosome breakage and polyploidy cell rates also implied the potential genotoxicity of AgNP. However, particle-specific toxicities and potential carcinogenic effect remain to be further confirmed in a chronic toxicity study.
AbstractList The potential risk of a nanoparticle as a medical application has raised wide concerns, and this study aims to investigate silver nanoparticle (AgNP)-induced acute toxicities, genotoxicities, target organs and the underlying mechanisms.OBJECTIVEThe potential risk of a nanoparticle as a medical application has raised wide concerns, and this study aims to investigate silver nanoparticle (AgNP)-induced acute toxicities, genotoxicities, target organs and the underlying mechanisms.Sprague-Dawley rats were randomly divided into 4 groups (n = 4 each group), and AgNP (containing Ag nanoparticles and released Ag+, 5 mg/kg), Ag+ (released from the same dose of AgNP, 0.0003 mg/kg), 5% sucrose solution (vechicle control) and cyclophophamide (positive control, 40 mg/kg) were administrated intravenously for 24 h respectively. Clinical signs and body weight of rats were recorded, and the tissues were subsequently collected for biochemical examination, Ag+ distribution detection, histopathological examination and genotoxicity assays.METHODSSprague-Dawley rats were randomly divided into 4 groups (n = 4 each group), and AgNP (containing Ag nanoparticles and released Ag+, 5 mg/kg), Ag+ (released from the same dose of AgNP, 0.0003 mg/kg), 5% sucrose solution (vechicle control) and cyclophophamide (positive control, 40 mg/kg) were administrated intravenously for 24 h respectively. Clinical signs and body weight of rats were recorded, and the tissues were subsequently collected for biochemical examination, Ag+ distribution detection, histopathological examination and genotoxicity assays.The rank of Ag detected in organs from highest to lowest is lung>spleen>liver>kidney>thymus>heart. Administration of AgNP induced a marked increase of ALT, BUN, TBil and Cre. Histopathological examination results showed that AgNP induced more extensive organ damages in liver, kidneys, thymus, and spleen. Bone marrow micronucleus assay found no statistical significance among groups (p > 0.05), but the number of aberration cells and multiple aberration cells were predominately increased from rats dosed with Ag+ and AgNP (p < 0.01), and more polyploidy cells were generated in the AgNP group (4.3%) compared with control.RESULTSThe rank of Ag detected in organs from highest to lowest is lung>spleen>liver>kidney>thymus>heart. Administration of AgNP induced a marked increase of ALT, BUN, TBil and Cre. Histopathological examination results showed that AgNP induced more extensive organ damages in liver, kidneys, thymus, and spleen. Bone marrow micronucleus assay found no statistical significance among groups (p > 0.05), but the number of aberration cells and multiple aberration cells were predominately increased from rats dosed with Ag+ and AgNP (p < 0.01), and more polyploidy cells were generated in the AgNP group (4.3%) compared with control.Our results indicated that the AgNP accumulated in the immune system organs, and mild irritation was observed in the thymus and spleen of animals treated with AgNP, but not with Ag+. The liver and kidneys could be the most affected organs by an acute i.v. dose of AgNP, and significantly increased chromosome breakage and polyploidy cell rates also implied the potential genotoxicity of AgNP. However, particle-specific toxicities and potential carcinogenic effect remain to be further confirmed in a chronic toxicity study.CONCLUSIONOur results indicated that the AgNP accumulated in the immune system organs, and mild irritation was observed in the thymus and spleen of animals treated with AgNP, but not with Ag+. The liver and kidneys could be the most affected organs by an acute i.v. dose of AgNP, and significantly increased chromosome breakage and polyploidy cell rates also implied the potential genotoxicity of AgNP. However, particle-specific toxicities and potential carcinogenic effect remain to be further confirmed in a chronic toxicity study.
Objective The potential risk of a nanoparticle as a medical application has raised wide concerns, and this study aims to investigate silver nanoparticle (AgNP)-induced acute toxicities, genotoxicities, target organs and the underlying mechanisms. Methods Sprague-Dawley rats were randomly divided into 4 groups (n = 4 each group), and AgNP (containing Ag nanoparticles and released Ag+, 5 mg/kg), Ag+ (released from the same dose of AgNP, 0.0003 mg/kg), 5% sucrose solution (vechicle control) and cyclophophamide (positive control, 40 mg/kg) were administrated intravenously for 24 h respectively. Clinical signs and body weight of rats were recorded, and the tissues were subsequently collected for biochemical examination, Ag+ distribution detection, histopathological examination and genotoxicity assays. Results The rank of Ag detected in organs from highest to lowest is lung>spleen>liver>kidney>thymus>heart. Administration of AgNP induced a marked increase of ALT, BUN, TBil and Cre. Histopathological examination results showed that AgNP induced more extensive organ damages in liver, kidneys, thymus, and spleen. Bone marrow micronucleus assay found no statistical significance among groups (p > 0.05), but the number of aberration cells and multiple aberration cells were predominately increased from rats dosed with Ag+ and AgNP (p < 0.01), and more polyploidy cells were generated in the AgNP group (4.3%) compared with control. Conclusion Our results indicated that the AgNP accumulated in the immune system organs, and mild irritation was observed in the thymus and spleen of animals treated with AgNP, but not with Ag+. The liver and kidneys could be the most affected organs by an acute i.v. dose of AgNP, and significantly increased chromosome breakage and polyploidy cell rates also implied the potential genotoxicity of AgNP. However, particle-specific toxicities and potential carcinogenic effect remain to be further confirmed in a chronic toxicity study.
The potential risk of a nanoparticle as a medical application has raised wide concerns, and this study aims to investigate silver nanoparticle (AgNP)-induced acute toxicities, genotoxicities, target organs and the underlying mechanisms. Sprague-Dawley rats were randomly divided into 4 groups (n = 4 each group), and AgNP (containing Ag nanoparticles and released Ag+, 5 mg/kg), Ag+ (released from the same dose of AgNP, 0.0003 mg/kg), 5% sucrose solution (vechicle control) and cyclophophamide (positive control, 40 mg/kg) were administrated intravenously for 24 h respectively. Clinical signs and body weight of rats were recorded, and the tissues were subsequently collected for biochemical examination, Ag+ distribution detection, histopathological examination and genotoxicity assays. The rank of Ag detected in organs from highest to lowest is lung>spleen>liver>kidney>thymus>heart. Administration of AgNP induced a marked increase of ALT, BUN, TBil and Cre. Histopathological examination results showed that AgNP induced more extensive organ damages in liver, kidneys, thymus, and spleen. Bone marrow micronucleus assay found no statistical significance among groups (p > 0.05), but the number of aberration cells and multiple aberration cells were predominately increased from rats dosed with Ag+ and AgNP (p < 0.01), and more polyploidy cells were generated in the AgNP group (4.3%) compared with control. Our results indicated that the AgNP accumulated in the immune system organs, and mild irritation was observed in the thymus and spleen of animals treated with AgNP, but not with Ag+. The liver and kidneys could be the most affected organs by an acute i.v. dose of AgNP, and significantly increased chromosome breakage and polyploidy cell rates also implied the potential genotoxicity of AgNP. However, particle-specific toxicities and potential carcinogenic effect remain to be further confirmed in a chronic toxicity study.
Objective The potential risk of a nanoparticle as a medical application has raised wide concerns, and this study aims to investigate silver nanoparticle (AgNP)-induced acute toxicities, genotoxicities, target organs and the underlying mechanisms. Methods Sprague-Dawley rats were randomly divided into 4 groups (n = 4 each group), and AgNP (containing Ag nanoparticles and released Ag.sup.+, 5 mg/kg), Ag.sup.+ (released from the same dose of AgNP, 0.0003 mg/kg), 5% sucrose solution (vechicle control) and cyclophophamide (positive control, 40 mg/kg) were administrated intravenously for 24 h respectively. Clinical signs and body weight of rats were recorded, and the tissues were subsequently collected for biochemical examination, Ag.sup.+ distribution detection, histopathological examination and genotoxicity assays. Results The rank of Ag detected in organs from highest to lowest is lung>spleen>liver>kidney>thymus>heart. Administration of AgNP induced a marked increase of ALT, BUN, TBil and Cre. Histopathological examination results showed that AgNP induced more extensive organ damages in liver, kidneys, thymus, and spleen. Bone marrow micronucleus assay found no statistical significance among groups (p > 0.05), but the number of aberration cells and multiple aberration cells were predominately increased from rats dosed with Ag.sup.+ and AgNP (p < 0.01), and more polyploidy cells were generated in the AgNP group (4.3%) compared with control. Conclusion Our results indicated that the AgNP accumulated in the immune system organs, and mild irritation was observed in the thymus and spleen of animals treated with AgNP, but not with Ag.sup.+ . The liver and kidneys could be the most affected organs by an acute i.v. dose of AgNP, and significantly increased chromosome breakage and polyploidy cell rates also implied the potential genotoxicity of AgNP. However, particle-specific toxicities and potential carcinogenic effect remain to be further confirmed in a chronic toxicity study.
The potential risk of a nanoparticle as a medical application has raised wide concerns, and this study aims to investigate silver nanoparticle (AgNP)-induced acute toxicities, genotoxicities, target organs and the underlying mechanisms. Sprague-Dawley rats were randomly divided into 4 groups (n = 4 each group), and AgNP (containing Ag nanoparticles and released Ag.sup.+, 5 mg/kg), Ag.sup.+ (released from the same dose of AgNP, 0.0003 mg/kg), 5% sucrose solution (vechicle control) and cyclophophamide (positive control, 40 mg/kg) were administrated intravenously for 24 h respectively. Clinical signs and body weight of rats were recorded, and the tissues were subsequently collected for biochemical examination, Ag.sup.+ distribution detection, histopathological examination and genotoxicity assays. The rank of Ag detected in organs from highest to lowest is lung>spleen>liver>kidney>thymus>heart. Administration of AgNP induced a marked increase of ALT, BUN, TBil and Cre. Histopathological examination results showed that AgNP induced more extensive organ damages in liver, kidneys, thymus, and spleen. Bone marrow micronucleus assay found no statistical significance among groups (p > 0.05), but the number of aberration cells and multiple aberration cells were predominately increased from rats dosed with Ag.sup.+ and AgNP (p < 0.01), and more polyploidy cells were generated in the AgNP group (4.3%) compared with control. Our results indicated that the AgNP accumulated in the immune system organs, and mild irritation was observed in the thymus and spleen of animals treated with AgNP, but not with Ag.sup.+ . The liver and kidneys could be the most affected organs by an acute i.v. dose of AgNP, and significantly increased chromosome breakage and polyploidy cell rates also implied the potential genotoxicity of AgNP. However, particle-specific toxicities and potential carcinogenic effect remain to be further confirmed in a chronic toxicity study.
Objective The potential risk of a nanoparticle as a medical application has raised wide concerns, and this study aims to investigate silver nanoparticle (AgNP)-induced acute toxicities, genotoxicities, target organs and the underlying mechanisms. Methods Sprague-Dawley rats were randomly divided into 4 groups ( n = 4 each group), and AgNP (containing Ag nanoparticles and released Ag + , 5 mg/kg), Ag + (released from the same dose of AgNP, 0.0003 mg/kg), 5% sucrose solution (vechicle control) and cyclophophamide (positive control, 40 mg/kg) were administrated intravenously for 24 h respectively. Clinical signs and body weight of rats were recorded, and the tissues were subsequently collected for biochemical examination, Ag + distribution detection, histopathological examination and genotoxicity assays. Results The rank of Ag detected in organs from highest to lowest is lung>spleen>liver>kidney>thymus>heart. Administration of AgNP induced a marked increase of ALT, BUN, TBil and Cre. Histopathological examination results showed that AgNP induced more extensive organ damages in liver, kidneys, thymus, and spleen. Bone marrow micronucleus assay found no statistical significance among groups ( p > 0.05), but the number of aberration cells and multiple aberration cells were predominately increased from rats dosed with Ag + and AgNP ( p < 0.01), and more polyploidy cells were generated in the AgNP group (4.3%) compared with control. Conclusion Our results indicated that the AgNP accumulated in the immune system organs, and mild irritation was observed in the thymus and spleen of animals treated with AgNP, but not with Ag + . The liver and kidneys could be the most affected organs by an acute i . v . dose of AgNP, and significantly increased chromosome breakage and polyploidy cell rates also implied the potential genotoxicity of AgNP. However, particle-specific toxicities and potential carcinogenic effect remain to be further confirmed in a chronic toxicity study.
The potential risk of a nanoparticle as a medical application has raised wide concerns, and this study aims to investigate silver nanoparticle (AgNP)-induced acute toxicities, genotoxicities, target organs and the underlying mechanisms.Sprague-Dawley rats were randomly divided into 4 groups (n = 4 each group), and AgNP (containing Ag nanoparticles and released Ag+, 5 mg/kg), Ag+ (released from the same dose of AgNP, 0.0003 mg/kg), 5% sucrose solution (vechicle control) and cyclophophamide (positive control, 40 mg/kg) were administrated intravenously for 24 h respectively. Clinical signs and body weight of rats were recorded, and the tissues were subsequently collected for biochemical examination, Ag+ distribution detection, histopathological examination and genotoxicity assays.The rank of Ag detected in organs from highest to lowest is lung>spleen>liver>kidney>thymus>heart. Administration of AgNP induced a marked increase of ALT, BUN, TBil and Cre. Histopathological examination results showed that AgNP induced more extensive organ damages in liver, kidneys, thymus, and spleen. Bone marrow micronucleus assay found no statistical significance among groups (p > 0.05), but the number of aberration cells and multiple aberration cells were predominately increased from rats dosed with Ag+ and AgNP (p < 0.01), and more polyploidy cells were generated in the AgNP group (4.3%) compared with control.Our results indicated that the AgNP accumulated in the immune system organs, and mild irritation was observed in the thymus and spleen of animals treated with AgNP, but not with Ag+. The liver and kidneys could be the most affected organs by an acute i.v. dose of AgNP, and significantly increased chromosome breakage and polyploidy cell rates also implied the potential genotoxicity of AgNP. However, particle-specific toxicities and potential carcinogenic effect remain to be further confirmed in a chronic toxicity study.
Audience Academic
Author Chen, Liang
Yang, Ying
Shao, Anliang
Dan, Mo
Lyu, Jianjun
Xu, Liming
Wen, Hairuo
Cheng, Xiang
AuthorAffiliation 1 National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Key Laboratory of Beijing for Nonclinical Safety Evaluation Research of Drugs, Beijing, P.R., China
2 Institute for Medical Device Control, National Institutes for Food and Drug Control, Beijing, P. R., China
3 Key Lab of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, China
Brandeis University, UNITED STATES
AuthorAffiliation_xml – name: 3 Key Lab of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, China
– name: Brandeis University, UNITED STATES
– name: 2 Institute for Medical Device Control, National Institutes for Food and Drug Control, Beijing, P. R., China
– name: 1 National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Key Laboratory of Beijing for Nonclinical Safety Evaluation Research of Drugs, Beijing, P.R., China
Author_xml – sequence: 1
  givenname: Hairuo
  surname: Wen
  fullname: Wen, Hairuo
– sequence: 2
  givenname: Mo
  surname: Dan
  fullname: Dan, Mo
– sequence: 3
  givenname: Ying
  surname: Yang
  fullname: Yang, Ying
– sequence: 4
  givenname: Jianjun
  surname: Lyu
  fullname: Lyu, Jianjun
– sequence: 5
  givenname: Anliang
  surname: Shao
  fullname: Shao, Anliang
– sequence: 6
  givenname: Xiang
  surname: Cheng
  fullname: Cheng, Xiang
– sequence: 7
  givenname: Liang
  surname: Chen
  fullname: Chen, Liang
– sequence: 8
  givenname: Liming
  orcidid: 0000-0003-2365-8000
  surname: Xu
  fullname: Xu, Liming
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28953974$$D View this record in MEDLINE/PubMed
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Snippet The potential risk of a nanoparticle as a medical application has raised wide concerns, and this study aims to investigate silver nanoparticle (AgNP)-induced...
Objective The potential risk of a nanoparticle as a medical application has raised wide concerns, and this study aims to investigate silver nanoparticle...
Objective The potential risk of a nanoparticle as a medical application has raised wide concerns, and this study aims to investigate silver nanoparticle...
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StartPage e0185554
SubjectTerms Aberration
Acute toxicity
Animal tissues
Animals
Archives & records
Biology and Life Sciences
Body weight
Bone marrow
Breakage
Carcinogens
Chronic toxicity
Damage
Deoxyribonucleic acid
DNA
Dosage
Drug dosages
Engineering and Technology
Female
Food
Gene expression
Genotoxicity
Heart
Hematology
Immune system
Irritation
Kidneys
Laboratories
Liver
Lungs
Medical equipment
Medical technology
Medicine and Health Sciences
Metal Nanoparticles - chemistry
Metal Nanoparticles - toxicity
Microscopy, Electron, Transmission
Mutagenicity Tests
Nanoparticles
Organs
Physiological aspects
Polyploidy
Rats
Rats, Sprague-Dawley
Rodents
Silver
Silver - chemistry
Spleen
Sucrose
Sugar
Thymus
Tissue Distribution
Toxicity
Toxicology
Transmission electron microscopy
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Title Acute toxicity and genotoxicity of silver nanoparticle in rats
URI https://www.ncbi.nlm.nih.gov/pubmed/28953974
https://www.proquest.com/docview/1947058005
https://www.proquest.com/docview/1944439421
https://pubmed.ncbi.nlm.nih.gov/PMC5617228
https://doaj.org/article/5c472053bf424a2c90f02eb97d2b36f7
http://dx.doi.org/10.1371/journal.pone.0185554
Volume 12
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