title: Proteomic analysis of urine in rats chronically exposed to fluoride.
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.
authors.affiliation: Bauru Dental School, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Claudia Ayumi Nakai
authors.initials: CA
authors.lastname: Kobayashi
authors.forename: Aline de Lima
authors.initials: Ade L
authors.lastname: Leite
authors.forename: Thelma Lopes
authors.initials: TL
authors.lastname: da Silva
authors.forename: Lucilene Delazari
authors.initials: LD
authors.lastname: dos Santos
authors.forename: Fábio César Sousa
authors.initials: FC
authors.lastname: Nogueira
authors.forename: Keity Souza
authors.initials: KS
authors.lastname: Santos
authors.forename: Rodrigo Cardoso
authors.initials: RC
authors.lastname: de Oliveira
authors.forename: Mario Sérgio
authors.initials: MS
authors.lastname: Palma
authors.forename: Gilberto Barbosa
authors.initials: GB
authors.lastname: Domont
authors.forename: Marília Afonso Rabelo
authors.initials: MA
authors.lastname: Buzalaf
mesh_terms: D000449:Aldehyde Reductase / Q000652:urine*; D000510:Alpha-Globulins / Q000187:drug effects / Q000652:urine*; D000818:Animals; D015415:Biomarkers / Q000652:urine; D015891:Cystatins; D015180:Electrophoresis, Gel, Two-Dimensional; D005459:Fluorides / Q000008:administration & dosage / Q000633:toxicity*; D009050:Fluorosis, Dental / Q000652:urine*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D014556:Urine / Q000737:chemistry*
chemical_list: D000510:Alpha-Globulins; C079958:Andpro protein, rat; D015415:Biomarkers; D015891:Cystatins; D011506:Proteins; C013803:alpha 2u globulin; C082765:aflatoxin B1 aldehyde reductase; D000449:Aldehyde Reductase; D005459:Fluorides