title: In vivo biodistribution and synergistic toxicity of silica nanoparticles and cadmium chloride in mice.
abstract: Silica nanoparticles (SiNPs) are now in daily use due to their low intrinsic toxicity. Cadmium is a ubiquitous environmental pollutant. In spite of real risk of humans' co-exposure to SiNPs and cadmium, their synergistic toxicity is still unclear. Here, we report the synergistic effects of SiNPs and CdCl₂ on their biodistribution and subacute toxicity in mice. The biodistributions, histopathological changes, serum biochemical parameters and oxidative stress responses were determined after intraperitoneal injection of SiNPs and/or CdCl₂ to mice. SiNPs and CdCl₂ have a positive synergistic toxicity in mice. Although SiNPs were low toxic to mice, co-exposure of SiNPs and CdCl₂ significantly enhanced CdCl₂-induced oxidative damage in the liver as indicated by the severe liver dysfunction and histopathological abnormalities. Co-exposure to SiNPs and CdCl₂ markedly increased the cadmium accumulation in the liver, which induced significant hepatic oxidative stress. In vitro binding assays indicated that serum albumin and Cd(2+) mutually enhanced the binding of each other to SiNPs via the interaction of serum albumin and Cd(2+). The uptake of serum albumin- and Cd(2+)-bound SiNPs by the macrophages significantly increased cadmium accumulation in mice. These results demonstrate that serum albumins play an important role in the positive synergistic toxicity of SiNPs and CdCl₂.
authors.affiliation: Department of Chemistry, University of Science and Technology of China, Hefei 230026, PR China.
authors.forename: Mingchun
authors.initials: M
authors.lastname: Guo
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Xu
authors.forename: Xincheng
authors.initials: X
authors.lastname: Yan
authors.forename: Shasha
authors.initials: S
authors.lastname: Wang
authors.forename: Shang
authors.initials: S
authors.lastname: Gao
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002104:Cadmium / Q000737:chemistry; D019256:Cadmium Chloride / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D004357:Drug Synergism; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008107:Liver Diseases / Q000503:physiopathology; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D036103:Nanotechnology; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D014018:Tissue Distribution
chemical_list: D015415:Biomarkers; D012709:Serum Albumin; D002104:Cadmium; D012822:Silicon Dioxide; D019256:Cadmium Chloride
keywords: Biodistribution; Cadmium; Oxidative stress; Silica nanoparticles; Synergistic toxicity