Proteomic Analysis of Liver in Rats Chronically Exposed to Fluoride

Author(s)

Barbosa da Silva Pereira, Heloisa Aparecida ^[1] ; Leite, Aline de Lima ^[1] ; Charone, Senda ^[1] ; Vaz Madureira Lobo, Janete Gualiume ^[1] ; Cestari, Tania Mary ^[1] ; Peres-Buzalaf, Camila ^[1] ; Rabelo Buzalaf, Marilia Afonso ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Biol Sci, Bauru Dent Sch, Sao Paulo - Brazil

• Document type: Journal article
• Source: PLoS One; v. 8, n. 9 SEP 17 2013.
• Web of Science Citations: 29

Abstract

Fluoride (F) is a potent anti-cariogenic element, but when ingestion is excessive, systemic toxicity may be observed. This can occur as acute or chronic responses, depending on both the amount of F and the time of exposure. The present study identified the profile of protein expression possibly associated with F-induced chronic hepatotoxicity. Weanling male Wistar rats (three-weeks old) were divided into three groups and treated with drinking water containing 0, 5 or 50 mg/L F for 60 days (n=6/group). At this time point, serum and livers were collected for F analysis, which was done using the ion-sensitive electrode, after hexamethyldisiloxane-facilitated diffusion. Livers were also submitted to histological and proteomic analyses (2D-PAGE followed by LC-MS/MS). Western blotting was done for confirmation of the proteomic data A dose-response was observed in serum F levels. In the livers, F levels were significantly increased in the 50 mg/L F group compared to groups treated with 0 and 5 mg/L F. Liver morphometric analysis did not reveal alterations in the cellular structures and lipid droplets were present in all groups. Proteomic quantitative intensity analysis detected 33, 44, and 29 spots differentially expressed in the comparisons between control vs. 5 mg/L F, control vs. 50 mg/L F, and 5 mg/L vs. 50 mg/L F, respectively. From these, 92 proteins were successfully identified. In addition, 18, 1, and 5 protein spots were shown to be exclusive in control, 5, and 50 mg/L F, respectively. Most of proteins were related to metabolic process and pronounced alterations were seen for the high-F level group. In F-treated rats, changes in the apolipoprotein E (ApoE) and GRP-78 expression may account for the F-induced toxicity in the liver. This can contribute to understanding the molecular mechanisms underlying hepatoxicity induced by F, by indicating key-proteins that should be better addressed in future studies. (AU)

• FAPESP's process: 08/07263-9 - Proteomic analysis in liver of rats submitted to chronic fluoride exposure
• Grantee: Heloisa Aparecida Barbosa da Silva Pereira
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 09/06892-5 - PROTEOMIC ANALYSIS IN LIVER OF RATS SUBMITTED TO CHRONIC FLUORIDE EXPOSURE
• Grantee: Marília Afonso Rabelo Buzalaf
• Support Opportunities: Regular Research Grants