title: Distribution and systemic effects of intranasally administered 25 nm silver nanoparticles in adult mice.
abstract: Previous work indicates that silver nanoparticles (AgNPs) given IP to mice alter the regulation of inflammation- and oxidative stress-related genes in brain. Here we assessed the distribution and toxic potential of AgNP following intranasal (IN) exposure. Adult male C57BL/6J mice received 25-nm AgNP (100 or 500 mg/kg) once IN. After 1 or 7 days, histopathology of selected organs was performed, and tissue reduced glutathione (GSH) levels were measured as an indicator of oxidative stress. Aggregated AgNP were found in spleen, lung, kidney, and nasal airway by routine light microscopy. Splenic AgNP accumulation was greatest in red pulp and occurred with modestly reduced cellularity and elevated hemosiderin deposition. Aggregated AgNP were not associated with microscopic changes in other tissues except for nasal mucosal erosions. Autometallography revealed AgNP in olfactory bulb and the lateral brain ventricles. Neither inflammatory cell infiltrates nor activated microglia were detected in brains of AgNP-treated mice. Elevated tissue GSH levels was observed in nasal epithelia (both doses at 1 day, 500 mg/kg at 7 days) and blood (500 mg/kg at 7 days). Therefore, IN administration of AgNP permits systemic distribution, produces reversible oxidative stress in the nose and in blood, and mildly enhances macrophage-mediated erythrocyte destruction in the spleen.
authors.affiliation: Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati, Cincinnati, Ohio 45267, USA. marybeth.genter@uc.edu
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Genter
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Newman
authors.forename: Howard G
authors.initials: HG
authors.lastname: Shertzer
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
authors.forename: Brad
authors.initials: B
authors.lastname: Bolon
mesh_terms: D000281:Administration, Intranasal; D000395:Air Pollutants, Occupational / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D018030:Silver Compounds / Q000493:pharmacokinetics* / Q000633:toxicity*; D014018:Tissue Distribution; D018675:Toxicity Tests
chemical_list: D000395:Air Pollutants, Occupational; D018030:Silver Compounds; D005978:Glutathione