title: Mast cell accumulation precedes tissue fibrosis induced by intravenously administered amorphous silica nanoparticles.
abstract: Despite the increasing use of amorphous silica nanoparticles (SNPs) in biomedical applications, their toxicity after intravenous administration remains a major concern. We investigated the effects of single 7 mg/kg intravenous infusions of 13 nm SNPs on hemodynamic parameters in rats. Hematological and biochemical parameters were assessed at 7, 30, and 60 d post treatment. Silicon content in the liver, lungs, heart, and kidney was analyzed, as well as tissue histology with special emphasis on mast cell (MC) content. SNP infusion had no effect on hemodynamics, nor did it alter hematological or biochemical parameters. SNP retention in the liver was conspicuous for up to 60 d. Among the other organs analyzed, silicon content was significantly increased only in the lung at 1-h post infusion. Despite the relatively low dose, SNP administration caused extensive liver remodeling, including the formation of multiple foreign body-type granulomas starting 7 d post treatment, and subsequent development of fibrosis. Histopathological changes in the liver were not preceded by hepatocyte necrosis. We found increased MC abundance in the liver, lungs, and heart starting on day 30 post treatment. MC recruitment in the liver preceded fibrosis, suggesting that MCs are involved in liver tissue remodeling elicited by intravenously administered SNPs.
authors.affiliation: a Institute of Experimental Medicine , Federal Almazov North-West Medical Research Centre , St. Petersburg , Russia ;|b Laboratory of Hearing and Speech, Core Research Centre , First I. P. Pavlov State Medical University of St. Petersburg , St. Petersburg , Russia ;
authors.forename: Serge
authors.initials: S
authors.lastname: Zhuravskii
authors.affiliation: c Division of Pathomorphology, Core Research Centre , First I. P. Pavlov State Medical University of St. Petersburg , St. Petersburg , Russia ;
authors.forename: Galina
authors.initials: G
authors.lastname: Yukina
authors.affiliation: a Institute of Experimental Medicine , Federal Almazov North-West Medical Research Centre , St. Petersburg , Russia ;|b Laboratory of Hearing and Speech, Core Research Centre , First I. P. Pavlov State Medical University of St. Petersburg , St. Petersburg , Russia ;
authors.forename: Olga
authors.initials: O
authors.lastname: Kulikova
authors.affiliation: a Institute of Experimental Medicine , Federal Almazov North-West Medical Research Centre , St. Petersburg , Russia ;|b Laboratory of Hearing and Speech, Core Research Centre , First I. P. Pavlov State Medical University of St. Petersburg , St. Petersburg , Russia ;
authors.forename: Alexey
authors.initials: A
authors.lastname: Panevin
authors.affiliation: c Division of Pathomorphology, Core Research Centre , First I. P. Pavlov State Medical University of St. Petersburg , St. Petersburg , Russia ;
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tomson
authors.affiliation: a Institute of Experimental Medicine , Federal Almazov North-West Medical Research Centre , St. Petersburg , Russia ;|d Department of Photonics and Optical Information Technology, ITMO University , St. Petersburg , Russia.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Korolev
authors.affiliation: a Institute of Experimental Medicine , Federal Almazov North-West Medical Research Centre , St. Petersburg , Russia ;|d Department of Photonics and Optical Information Technology, ITMO University , St. Petersburg , Russia.
authors.forename: Michael
authors.initials: M
authors.lastname: Galagudza
mesh_terms: D000818:Animals; D015745:Granuloma, Foreign-Body / Q000139:chemically induced; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D014018:Tissue Distribution
chemical_list: D012822:Silicon Dioxide
keywords: Fibrosis; granuloma; mast cells; silica nanoparticles; toxicity