Proposed mechanism for understanding the dose-and time-dependency of the effects of fluoride in the liver

Author(s)

Barbosa da Silva Pereira, Heloisa Aparecida ^[1] ; Dionizio, Aline Salgado ^[2] ; Araujo, Tamara Teodoro ^[2] ; Fernandes, Mileni da Silva ^[1] ; Iano, Flavia Godoy ^[2] ; Rabelo Buzalaf, Marilia Afonso ^[2]

Affiliation

^[1] Univ Fed Sao Carlos, Ctr Biol Sci & Hlth, Dept Genet & Evolut, Washington Luis, Km 235, BR-13560970 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Bauru Dent Sch, Dept Biol Sci, Al Octavio Pinheiro Brisolla 9-75, BR-17012901 Sao Paulo - Brazil

• Document type: Journal article
• Source: Toxicology and Applied Pharmacology; v. 358, p. 68-75, NOV 1 2018.
• Web of Science Citations: 3

Abstract

Fluoride (F) can induce changes in the expression of several liver proteins. It is suggested that these changes are dose- and time-dependent. The objective of this study was to analyze the effect of different F concentrations and exposure times to this ion on the pattern of protein expression in the liver of rats. Thirt-six 21-day-old male Wistar rats were divided into 2 groups (n = 18) according to the treatment duration (20 or 60 days). Each of these groups was then divided into 3 subgroups (n = 6) according to the concentration of F administered in drinking water, as follows: 0 mg/L (control), 15 mg/L or 50 mg/L. After the experiment periods, the animals were anesthetized and the liver and blood were collected. F was analyzed in plasma and liver. Part of the liver was fixed for histological analysis. Liver proteins were extracted and prepared for quantitative label-free mass spectrometry analysis. F concentrations in plasma and liver were significantly higher in the group treated with 50 mg /L in comparison with control, regardless the time of exposure. Histological alterations in the liver were more evident in the subgroups treated for 20 days. The proteomic analysis revealed changes in proteins related to endoplasmic reticulum and mitochondrial oxidative stress, mitochondrial alteration, apoptosis and cellular respiration upon exposure to F. The results reinforce previous findings showing that the effects of F in the liver are dose- and time-dependent and provide the molecular basis for understanding the evolution of these effects. (AU)

• FAPESP's process: 12/16840-5 - Fluoride toxicology: proteomic studies in gut and liver
• Grantee: Marília Afonso Rabelo Buzalaf
• Support type: Regular Research Grants
• FAPESP's process: 11/17263-9 - Effect of treatment time and dose of fluoride chronically administered on protein expression in the liver of rats
• Grantee: Heloisa Aparecida Barbosa da Silva Pereira
• Support type: Scholarships in Brazil - Doctorate