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Fluoride toxicology: proteomic studies in gut and liver

Abstract

The gastro-intestinal tract is the main route of exposure to fluoride (F), which is rapidly absorbed. The complex coordination of the intestinal function is made by autonomous interlinked neuronal networks present in the walls of the intestin. This systems is called enteric nervous system (ENS). Despite the neurotoxic effects of F on the central nervous system are widely described in the literature, there are no reports on the neurotoxicity of F on the ENS. In a previous study conducted by our group it was observed that fluoride can cause alterations in the expression of many hepatic proteins. In addition, it has been reported that these alterations are dose- and time-dependent. The present study will be developed as 2 projects that aim: (1) to evaluate the efefct of chronic and acute exposure to F on the general population of enteric neurons and also on specific populations that express the main neurotransmitters, such as nitric oxide (NO), vasoactive intestinal peptide (VIP), acetylcholine (ACh), calcitonin gene related peptide (CGRP) and P substance (SP), as well as to establish the differential proteomic profile in the intestin of the different treatment groups; (2) to analyze the alterations in the liver of rats submitted to chronic fluoride exposure in different times and doses, using proteomic and histological analyses. In the first part of the project, the animals will be divided into 5 groups that will receive chronic doses of 0, 5 or 50 ppm F for 30 days in the drinking water, while the acute dose will be 0 or 100 mgF/Kg body weight (gastric gavage). At the end of the treatment, the rats will be euthanized in order to collect samples (small intestin) for immunohistochemical analysis. Proteomic analysis of the small intestin will also be conducted in attempt to better investigate and integrate the phenomena that will be observed. In the second part of the project, the animals will be divided into 2 groups, according to the time of treatment (20 days, group A, or 60 days, group B). Each group will be divided into 3 smaller groups. according to the dose of fluoride to be administered through the drinking water, as follows: 0 (control - groups A1 and B1), 15 (groups A2 and B2) or 50 mg/L (groups A3 and B3). At the end of the treatment, the animals will be euthanized and the liver will be submitted to proteomic, histological and fluoride analysis. (AU)

Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE SOUZA MELO, CARINA GUIMARAES; ZANONI, JACQUELINE NELISIS; GARCIA DE SOUZA, SARA RAQUEL; ZIGNANI, ISABELA; LEITE, ALINE DE LIMA; HEUBEL, ALESSANDRO DOMINGUES; COLOMBO MARTINS PERLES, JULIANA VANESSA; RABELO BUZALAF, MARILIA AFONSO. Global Proteomic Profile Integrated to Quantitative and Morphometric Assessment of Enteric Neurons: Investigation of the Mechanisms Involved in the Toxicity Induced by Acute Fluoride Exposure in the Duodenum. NEUROTOXICITY RESEARCH, v. 39, n. 3 MAR 2021. Web of Science Citations: 0.
DIONIZIO, ALINE; MELO, CARINA GUIMARAES SOUZA; SABINO-ARIAS, ISABELA TOMAZINI; ARAUJO, TAMARA TEODORO; VENTURA, TALITA MENDES OLIVEIRA; LEITE, ALINE LIMA; SOUZA, SARA RAQUEL GARCIA; SANTOS, ERIKA XAVIER; HEUBEL, ALESSANDRO DOMINGUES; SOUZA, JULIANA GADELHA; PERLES, JULIANA VANESSA COLOMBO MARTINS; ZANONI, JACQUELINE NELISIS; BUZALAF, MARILIA AFONSO RABELO. Effects of acute fluoride exposure on the jejunum and ileum of rats: Insights from proteomic and enteric innervation analysis. Science of The Total Environment, v. 741, NOV 1 2020. Web of Science Citations: 0.
BARBOSA DA SILVA PEREIRA, HELOISA APARECIDA; DIONIZIO, ALINE SALGADO; ARAUJO, TAMARA TEODORO; FERNANDES, MILENI DA SILVA; IANO, FLAVIA GODOY; RABELO BUZALAF, MARILIA AFONSO. Proposed mechanism for understanding the dose-and time-dependency of the effects of fluoride in the liver. Toxicology and Applied Pharmacology, v. 358, p. 68-75, NOV 1 2018. Web of Science Citations: 3.
DIONIZIO, ALINE SALGADO; SOUZA MELO, CARINA GUIMARAES; SABINO-ARIAS, ISABELA TOMAZINI; SILVA VENTURA, TALITA MENDES; LEITE, ALINE LIMA; GARCIA SOUZA, SARA RAQUEL; SANTOS, ERIKA XAVIER; HEUBEL, ALESSANDRO DOMINGUES; SOUZA, JULIANA GADELHA; COLOMBO MARTINS PERLES, JULIANA VANESSA; ZANONI, JACQUELINE NELISIS; RABELO BUZALAF, MARILIA AFONSO. Chronic treatment with fluoride affects the jejunum: insights from proteomics and enteric innervation analysis. SCIENTIFIC REPORTS, v. 8, FEB 16 2018. Web of Science Citations: 3.
DE SOUZA MELO, CARINA GUIMARAES; COLOMBO MARTINS PERLES, JULIANA VANESSA; ZANONI, JACQUELINE NELISIS; GARCIA DE SOUZA, SARA RAQUEL; SANTOS, ERIKA XAVIER; LEITE, ALINE DE LIMA; HEUBEL, ALESSANDRO DOMINGUES; OLIVEIRA E SOUZA, CAMILA; DE SOUZA, JULIANA GADELHA; RABELO BUZALAF, MARILIA AFONSO. Enteric innervation combined with proteomics for the evaluation of the effects of chronic fluoride exposure on the duodenum of rats. SCIENTIFIC REPORTS, v. 7, APR 21 2017. Web of Science Citations: 8.

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