Proteomic analysis of urine in rats chronically exposed to fluoride

J Biochem Mol Toxicol. 2011 Jan-Feb;25(1):8-14. doi: 10.1002/jbt.20353.

Abstract

Urine is an ideal source of materials to search for potential disease-related biomarkers as it is produced by the affected tissues and can be easily obtained by noninvasive methods. 2-DE-based proteomic approach was used to better understand the molecular mechanisms of injury induced by fluoride (F(-)) and define potential biomarkers of dental fluorosis. Three groups of weanling male Wistar rats were treated with drinking water containing 0 (control), 5, or 50 ppm F(-) for 60 days (n = 15/group). During the experimental period, the animals were kept individually in metabolic cages, to analyze the water and food consumption, as well as fecal and urinary F(-) excretion. Urinary proteome profiles were examined using 2-DE and Colloidal Coomassie Brilliant Blue staining. A dose-response regarding F(-) intake and excretion was detected. Quantitative intensity analysis revealed 8, 11, and 8 significantly altered proteins between control vs. 5 ppm F(-), control vs. 50 ppm F(-) and 5 ppm F(-) vs. 50 ppm F(-) groups, respectively. Two proteins regulated by androgens (androgen-regulated 20-KDa protein and α-2μ-globulin) and one related to detoxification (aflatoxin-B1-aldehyde-reductase) were identified by MALDI-TOF-TOF MS/MS. Thus, proteomic analysis can help to better understand the mechanisms underlying F(-) toxicity, even in low doses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Reductase / urine*
  • Alpha-Globulins / drug effects
  • Alpha-Globulins / urine*
  • Animals
  • Biomarkers / urine
  • Cystatins
  • Electrophoresis, Gel, Two-Dimensional
  • Fluorides / administration & dosage
  • Fluorides / toxicity*
  • Fluorosis, Dental / urine*
  • Male
  • Mass Spectrometry / methods
  • Proteins / metabolism*
  • Proteomics / methods
  • Rats
  • Rats, Wistar
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods
  • Urine / chemistry*

Substances

  • Alpha-Globulins
  • Andpro protein, rat
  • Biomarkers
  • Cystatins
  • Proteins
  • alpha 2u globulin
  • aflatoxin B1 aldehyde reductase
  • Aldehyde Reductase
  • Fluorides