title: Potential neurological lesion after nasal instillation of TiO(2) nanoparticles in the anatase and rutile crystal phases.
abstract: Nanoscale titanium dioxide (TiO(2)) is massively produced and widely used in living environment, which hence make the potential risk to human health. Central nervous system (CNS) is the potential susceptible target of inhaled nanoparticles, but the studies on this aspect are limited so far. We report the accumulation and toxicity results in vivo of two crystalline phases of TiO(2) nanoparticles (80nm, rutile and 155nm, anatase; purity >99%). The female mice were intranasally instilled with 500microg of TiO(2) nanoparticles suspension every other day for 30 days. Synchrotron radiation X-ray fluorescence analysis (SRXRF) and inductively coupled plasma mass spectrometry (ICP-MS) were used to determine the contents of titanium in murine brain. Then, the pathological examination of brain tissue, oxidative stress-mediated responses, and levels of neurochemicals in the brain of exposed mice were also analyzed. The obvious morphological changes of hippocampal neurons and increased GFAP-positive astrocytes in the CA4 region were observed, which were in good agreements with higher Ti contents in the hippocampus region. Oxidative stress occurred obviously in whole brain of exposed mice such as lipid peroxidation, protein oxidation and increased activities of catalase, as well as the excessive release of glutamic acid and nitric oxide. These findings indicate anatase TiO(2) nanoparticles exhibited higher concern on some tested biological effects. To summarize, results provided the preliminary evidence that nasal instilled TiO(2) nanoparticles could be translocated into the central nervous system and cause potential lesion of brain, and the hippocampus would be the main target within brain.
authors.affiliation: Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Lab of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Jiangxue
authors.initials: J
authors.lastname: Wang
authors.forename: Chunying
authors.initials: C
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Jiao
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Lao
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Li
authors.forename: Bai
authors.initials: B
authors.lastname: Li
authors.forename: Cuicui
authors.initials: C
authors.lastname: Ge
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhou
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Gao
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Chai
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000281:Administration, Intranasal; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D003460:Crystallization; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008813:Mice, Inbred ICR; D008953:Models, Anatomic; D053758:Nanoparticles / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity*; D009417:Nerve Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009422:Nervous System Diseases / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D013052:Spectrometry, X-Ray Emission / Q000379:methods; D017356:Synchrotrons; D014025:Titanium / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity*
chemical_list: D009419:Nerve Tissue Proteins; C009495:titanium dioxide; D009569:Nitric Oxide; D018698:Glutamic Acid; D014025:Titanium; D000110:Acetylcholinesterase