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

The enteric nervous system is responsible for controlling the gastrointestinal tract (GIT) functions. Enteric neuropathies are highly correlated to the development of several intestinal disturbances. Fluoride (F) is extensively applied for dental health improvement and its ingestion can promote syst...

Full description

Saved in:
Bibliographic Details
Published in:Neurotoxicity research 2021-06, Vol.39 (3), p.800-814
Main Authors: Guimaraes de Souza Melo, Carina, Nelisis Zanoni, Jacqueline, Raquel Garcia de Souza, Sara, Zignani, Isabela, de Lima Leite, Aline, Domingues Heubel, Alessandro, Vanessa Colombo Martins Perles, Juliana, Afonso Rabelo Buzalaf, Marília
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Cell Biology
Neurobiology
Neurochemistry
Neurology
Neurosciences
Original Article
Pharmacology/Toxicology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The enteric nervous system is responsible for controlling the gastrointestinal tract (GIT) functions. Enteric neuropathies are highly correlated to the development of several intestinal disturbances. Fluoride (F) is extensively applied for dental health improvement and its ingestion can promote systemic toxicity with mild to severe GIT symptomatology and neurotoxicity. Although F harmful effects have been published, there is no information regarding noxiousness of a high acute F exposure (25 mg F/kg) on enteric neurons and levels of expression of intestinal proteins in the duodenum. Quantitative proteomics of the duodenum wall associated to morphometric and quantitative analysis of enteric neurons displayed F effects of a high acute exposure. F-induced myenteric neuroplasticity was characterized by a decrease in the density of nitrergic neurons and morphometric alterations in the general populations of neurons, nitrergic neurons, and substance P varicosities. Proteomics demonstrated F-induced alterations in levels of expression of 356 proteins correlated to striated muscle cell differentiation; generation of precursor metabolites and energy; NADH and glutathione metabolic process and purine ribonucleoside triphosphate biosynthesis. The neurochemical role of several intestinal proteins was discussed specially related to the modulation of enteric neuroplasticity. The results provide a new perspective on cell signaling pathways of gastrointestinal symptomatology promoted by acute F toxicity.
ISSN:1029-8428
1476-3524
DOI:10.1007/s12640-020-00296-9