title: Intragastric exposure to titanium dioxide nanoparticles induced nephrotoxicity in mice, assessed by physiological and gene expression modifications.
abstract: BACKGROUND
  Numerous studies have demonstrated that titanium dioxide nanoparticles (TiO2 NPs) induced nephrotoxicity in animals. However, the nephrotoxic multiple molecular mechanisms are not clearly understood.
  
  
  METHODS
  Mice were exposed to 2.5, 5 and 10 mg/kg TiO2 NPs by intragastric administration for 90 consecutive days, and their growth, element distribution, and oxidative stress in kidney as well as kidney gene expression profile were investigated using whole-genome microarray analysis technique.
  
  
  RESULTS
  Our findings suggest that TiO2 NPs resulted in significant reduction of renal glomerulus number, apoptosis, infiltration of inflammatory cells, tissue necrosis or disorganization of renal tubules, coupled with decreased body weight, increased kidney indices, unbalance of element distribution, production of reactive oxygen species and peroxidation of lipid, protein and DNA in mouse kidney tissue. Furthermore, microarray analysis showed significant alterations in the expression of 1, 246 genes in the 10 mg/kg TiO2 NPs-exposed kidney. Of the genes altered, 1006 genes were associated with immune/inflammatory responses, apoptosis, biological processes, oxidative stress, ion transport, metabolic processes, the cell cycle, signal transduction, cell component, transcription, translation and cell differentiation, respectively. Specifically, the vital up-regulation of Bcl6, Cfi and Cfd caused immune/ inflammatory responses, the significant alterations of Axud1, Cyp4a12a, Cyp4a12b, Cyp4a14, and Cyp2d9 expression resulted in severe oxidative stress, and great suppression of Birc5, Crap2, and Tfrc expression led to renal cell apoptosis.
  
  
  CONCLUSIONS
  Axud1, Bcl6, Cf1, Cfd, Cyp4a12a, Cyp4a12b, Cyp2d9, Birc5, Crap2, and Tfrc may be potential biomarkers of kidney toxicity caused by TiO2 NPs exposure.
authors: Medical College of Soochow University, Suzhou 215123, China.
authors: Suxin
authors: S
authors: Gui
authors: Xuezi
authors: X
authors: Sang
authors: Lei
authors: L
authors: Zheng
authors: Yuguan
authors: Y
authors: Ze
authors: Xiaoyang
authors: X
authors: Zhao
authors: Lei
authors: L
authors: Sheng
authors: Qingqing
authors: Q
authors: Sun
authors: Zhe
authors: Z
authors: Cheng
authors: Jie
authors: J
authors: Cheng
authors: Renping
authors: R
authors: Hu
authors: Ling
authors: L
authors: Wang
authors: Fashui
authors: F
authors: Hong
authors: Meng
authors: M
authors: Tang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007674:Kidney Diseases / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D013499:Surface Properties; D014025:Titanium / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
chemical_list: C009495:titanium dioxide; D014025:Titanium