title: Metabonomic studies of biochemical changes in the serum of rats by intratracheally instilled TiO2 nanoparticles.
abstract: In vivo behavior of nanoparticles and interactions between nanoparticles and organisms are key components of nanotoxicology. In this study, the biochemical compositions of rat serum exposed to TiO2 nanoparticles (nano-TiO2) by intratracheal instillation at low (0.8 mg/kg), medium (4 mg/kg) and high doses (20 mg/kg) were investigated using 1H-NMR techniques with pattern recognition methods. Serum biochemical assays, as well as histopathological and transmission electron microscopy (TEM) examinations of tissues were performed. 1H-NMR spectra and pattern recognition analyses of nano-TiO2 treated animals showed increased serum levels of ketone bodies, choline, low density lipoprotein (LDL), alanine and GLU, and decreased levels of lactate, creatine and pyruvate. Clinical chemistry analyses of serum showed increased levels of lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase, as well as increased levels of blood urea nitrogen and creatinine, indicating slight liver and kidney injury. Furthermore, TEM provided an analysis of particle-related structural changes of the lungs, liver and kidneys, and revealed that the localization of nanoparticles within cells induced apoptosis. The damage to the target organs was associated with the perturbation of energy metabolism. Serum 1H-NMR spectra, in combination with pattern recognition techniques, proved to be an efficient and simple metabonomic method to depict the metabolic changes produced by intratracheally-instilled nano-TiO2.
authors.affiliation: Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Tang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Yuying
authors.initials: Y
authors.lastname: Xue
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Mingming
authors.initials: M
authors.lastname: Huang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Minyu
authors.initials: M
authors.lastname: Lu
authors.forename: Hao
authors.initials: H
authors.lastname: Lei
authors.forename: Lu
authors.initials: L
authors.lastname: Kong
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuepu
authors.initials: Y
authors.lastname: Pu
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D008657:Metabolic Clearance Rate; D049329:Nanostructures / Q000008:administration & dosage / Q000032:analysis* / Q000737:chemistry*; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014025:Titanium / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: C009495:titanium dioxide; D014025:Titanium