Systemic and behavioral effects of intranasal administration of silver nanoparticles.
Use of silver nanoparticles (AgNPs) for their antimicrobial properties is widespread. Much of the previous work on the toxicity of AgNPs has been conducted in vitro or following oral or intravenous administration in vivo. Intranasal (IN) instillation of AgNPs mimics inhalation exposure and allows further exploration of the toxicity of these particles via respiratory tract exposure. The present study involved 1) single-dose exposures to assess tissue distribution and toxicity and 2) repeated exposures to assess behavioral effects of IN AgNP exposure (nominally uncoated 25 nm AgNP). AgNP deposition was localized in the liver, gut-associated lymphoid tissue, and brain. Decrease cellularity in spleen follicles was observed in treated mice, along with changes in cell number and populations in the spleen. The splenic GSH:GSSG ratio was also reduced following AgNP exposure. Expression of the oxidative stress-responsive gene Hmox1 was elevated in the hippocampus, but not cortex of treated mice, as was the level of HMOX1 protein. Mice receiving 7 days of IN exposure to 50 mg/kg AgNPs exhibited similar learning- and memory-related behaviors to control mice, except that treated mice spent significantly less time in the target quadrant of the Morris Water Maze during the acquisition phase probe trial. These findings indicate systemic distribution and toxicity following IN administration of AgNPs.
Department of Environmental Health, University of Cincinnati, 160 Panzeca Way, Cincinnati, OH 45267 USA.
Laurie L
LL
Davenport
Department of Environmental Health, University of Cincinnati, 160 Panzeca Way, Cincinnati, OH 45267 USA.
Heidi
H
Hsieh
Department of Environmental Health, University of Cincinnati, 160 Panzeca Way, Cincinnati, OH 45267 USA.
Bryan L
BL
Eppert
Department of Environmental Health, University of Cincinnati, 160 Panzeca Way, Cincinnati, OH 45267 USA.
Vinicius S
VS
Carreira
Department of Environmental Health, University of Cincinnati, 160 Panzeca Way, Cincinnati, OH 45267 USA.
Mansi
M
Krishan
NCTR/ORA Nanotechnology Core Facility, 3900 NCTR Rd., Jefferson, AR 72079, USA.
Taylor
T
Ingle
NCTR/ORA Nanotechnology Core Facility, 3900 NCTR Rd., Jefferson, AR 72079, USA.
Paul C
PC
Howard
Division of Child Neurology (MLC 7044), Cincinnati Children's Research Foundation, 3333 Burnet Ave., Cincinnati, OH 45229 USA.
Michael T
MT
Williams
Division of Child Neurology (MLC 7044), Cincinnati Children's Research Foundation, 3333 Burnet Ave., Cincinnati, OH 45229 USA.
Charles V
CV
Vorhees
Department of Environmental Health, University of Cincinnati, 160 Panzeca Way, Cincinnati, OH 45267 USA. Electronic address: Marybeth.genter@uc.edu.
Mary Beth
MB
Genter
D000281:Administration, Intranasal; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D020547:Lateral Ventricles / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D021641:Recognition, Psychology / Q000187:drug effects* / Q000502:physiology; D018030:Silver Compounds / Q000633:toxicity*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D014018:Tissue Distribution / Q000187:drug effects
D018030:Silver Compounds; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat
Autometallography; Intranasal instillation; Morris Water Maze; Neurobehavioral effects; Silver nanoparticles