title: Biological responses to perfluorododecanoic acid exposure in rat kidneys as determined by integrated proteomic and metabonomic studies.
abstract: BACKGROUND
  Perfluorododecanoic acid (PFDoA) is a perfluorinated carboxylic chemical (PFC) that has broad applications and distribution in the environment. While many studies have focused on hepatotoxicity, immunotoxicity, and reproductive toxicity of PFCAs, few have investigated renal toxicity.
  
  
  RESULTS
  Here, we used comparative proteomic and metabonomic technologies to provide a global perspective on renal response to PFDoA. Male rats were exposed to 0, 0.05, 0.2, and 0.5 mg/kg/day of PFDoA for 110 days. After 2-D DIGE and MALDI TOF/TOF analysis, 79 differentially expressed proteins between the control and the PFDoA treated rats (0.2 and 0.5 mg-dosed groups) were successfully identified. These proteins were mainly involved in amino acid metabolism, the tricarboxylic acid cycle, gluconeogenesis, glycolysis, electron transport, and stress response. Nuclear magnetic resonance-based metabonomic analysis showed an increase in pyruvate, lactate, acetate, choline, and a variety of amino acids in the highest dose group. Furthermore, the profiles of free amino acids in the PFDoA treated groups were investigated quantitatively by high-coverage quantitative iTRAQ-LC MS/MS, which showed levels of sarcosine, asparagine, histidine, 1-methylhistidine, Ile, Leu, Val, Trp, Tyr, Phe, Cys, and Met increased markedly in the 0.5 mg dosed group, while homocitrulline, α-aminoadipic acid, β-alanine, and cystathionine decreased.
  
  
  CONCLUSIONS
  These observations provide evidence that disorders in glucose and amino acid metabolism may contribute to PFDoA nephrotoxicity. Additionally, α(2u) globulin may play an important role in protecting the kidneys from PFDoA toxicity.
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhang
authors.forename: Lina
authors.initials: L
authors.lastname: Ding
authors.forename: Xuemei
authors.initials: X
authors.lastname: Fang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Shi
authors.forename: Yating
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hebing
authors.initials: H
authors.lastname: Chen
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Yan
authors.forename: Jiayin
authors.initials: J
authors.lastname: Dai
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004734:Energy Metabolism / Q000187:drug effects; D005466:Fluorocarbons; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D007850:Lauric Acids / Q000494:pharmacology*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D019906:Nuclear Magnetic Resonance, Biomolecular; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D000596:Amino Acids; D005466:Fluorocarbons; D007850:Lauric Acids; C522391:perfluorododecanoic acid