Proposed mechanism for understanding the dose- and time-dependency of the effects of fluoride in the liver
| Autor: | Aline Dionizio, Tamara Teodoro Araujo, Mileni da Silva Fernandes, Marília Afonso Rabelo Buzalaf, Flávia Godoy Iano, Heloísa Aparecida Barbosa da Silva Pereira |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Time Factors Cellular respiration Treatment duration 010501 environmental sciences Toxicology medicine.disease_cause 01 natural sciences Mitochondrial alteration Fluorides 03 medical and health sciences chemistry.chemical_compound Internal medicine medicine Animals Time dependency Rats Wistar 0105 earth and related environmental sciences Pharmacology Dose-Response Relationship Drug Drinking Water Endoplasmic reticulum RATOS WISTAR Rats 030104 developmental biology Endocrinology Liver chemistry Apoptosis Fluoride Oxidative stress |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2018.09.010 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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